Neuropathy target esterase: Difference between revisions

From Wikipedia, the free encyclopedia
Browse history interactively
← Previous edit
Content deleted Content added
VisualWikitext
Cite error - ref name "pmid9576844" defined multiple times.- Fixed.
m added display-authors=6 to the main template, removed trailing whitespaces
 
(29 intermediate revisions by 16 users not shown)
Line 1: Line 1:
{{Short description|Protein-coding gene in the species Homo sapiens}}
{{PBB|geneid=10908}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
⚫
'''Neuropathy target esterase''' also known as '''patatin-like phospholipase domain-containing protein 6''' (PNPLA6) is a neuropathy target esterase [[enzyme]] that in humans is encoded by the ''PNPLA6'' [[gene]].<ref name="pmid9576844">{{cite journal | author = Lush MJ, Li Y, Read DJ, Willis AC, Glynn P | title = Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man | series = 332 | journal = Biochem J | volume = ( Pt 1) | issue = | pages = 1–4 |date=Aug 1998 | pmid = 9576844 | pmc = 1219444 | doi = }}</ref><ref name="pmid16799181">{{cite journal | author = Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ | title = Characterization of the human patatin-like phospholipase family | journal = J Lipid Res | volume = 47 | issue = 9 | pages = 1940–9 |date=Aug 2006 | pmid = 16799181 | pmc = | doi = 10.1194/jlr.M600185-JLR200 }}</ref><ref name="pmid19029121">{{cite journal | author = Kienesberger PC, Oberer M, Lass A, Zechner R | title = Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions | journal = J Lipid Res | volume = 50 Suppl | issue = Supplement| pages = S63–8 |date=Apr 2009 | pmid = 19029121 | pmc = 2674697 | doi = 10.1194/jlr.R800082-JLR200 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10908| accessdate = }}</ref>
{{Infobox_gene}}
⚫
'''Neuropathy target esterase''', also known as '''patatin-like phospholipase domain-containing protein 6''' (PNPLA6), is an [[esterase]] enzyme that in humans is encoded by the ''PNPLA6'' [[gene]].<ref name="pmid9576844">{{cite journal |vauthors=Lush MJ, Li Y, Read DJ, Willis AC, Glynn P | title = Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man | series = 332 | journal = Biochem J | volume = ( Pt 1) | pages = 1–4 |date=Aug 1998 | issue = Pt 1 | pmid = 9576844 | pmc = 1219444 | doi = 10.1042/bj3320001}}</ref><ref name="pmid16799181">{{cite journal |vauthors=Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ | title = Characterization of the human patatin-like phospholipase family | journal = J Lipid Res | volume = 47 | issue = 9 | pages = 1940–9 |date=Aug 2006 | pmid = 16799181 | doi = 10.1194/jlr.M600185-JLR200 | doi-access = free }}</ref><ref name="pmid19029121">{{cite journal |vauthors=Kienesberger PC, Oberer M, Lass A, Zechner R | title = Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions | journal = J Lipid Res | volume = 50 Suppl | issue = Supplement| pages = S63–8 |date=Apr 2009 | pmid = 19029121 | pmc = 2674697 | doi = 10.1194/jlr.R800082-JLR200 |doi-access=free }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=10908}}</ref>


Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce [[glycerophosphocholine]]. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.<ref name="entrez"/>
Neuropathy target esterase is a [[phospholipase]] that deacetylates intracellular [[phosphatidylcholine]] to produce [[glycerophosphocholine]]. It is thought to function in [[neurite outgrowth]] and process elongation during [[neuronal differentiation]]. The protein is anchored to the cytoplasmic face of the [[endoplasmic reticulum]] in both neurons and non-neuronal cells.<ref name="entrez"/>


== Function ==
== Function ==
Neuropathy target esterase is an enzyme with [[phospholipase B]] activity: It sequentially hydrolyses both fatty acids from the major membrane lipid [[phosphatidylcholine]], which generates water-soluble glycerophosphocholine.<ref name="pmid16137924">{{cite journal | author = Glynn P | title = Neuropathy target esterase and phospholipid deacylation | journal = Biochim. Biophys. Acta | volume = 1736 | issue = 2 | pages = 87–93 |date=September 2005 | pmid = 16137924 | doi = 10.1016/j.bbalip.2005.08.002 }}</ref><ref name="pmid16731034">{{cite journal | author = Fernández-Murray JP, McMaster CR | title = Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1 | journal = Biochim. Biophys. Acta | volume = 1771 | issue = 3 | pages = 331–6 |date=March 2007 | pmid = 16731034 | doi = 10.1016/j.bbalip.2006.04.004 }}</ref> In cells of eukaryotes from yeast to humans, NTE is anchored to the cytoplasmic face of the [[endoplasmic reticulum]] membrane and is particularly abundant in neurons, the placenta, and the kidney.<ref name="pmid12514188">{{cite journal | author = Li Y, Dinsdale D, Glynn P | title = Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells | journal = J. Biol. Chem. | volume = 278 | issue = 10 | pages = 8820–5 |date=March 2003 | pmid = 12514188 | doi = 10.1074/jbc.M210743200 }}</ref><ref name="pmid15044461">{{cite journal | author = Zaccheo O, Dinsdale D, Meacock PA, Glynn P | title = Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells | journal = J. Biol. Chem. | volume = 279 | issue = 23 | pages = 24024–33 |date=June 2004 | pmid = 15044461 | doi = 10.1074/jbc.M400830200 }}</ref><ref name="pmid9466418">{{cite journal | author = Glynn P, Holton JL, Nolan CC, Read DJ, Brown L, Hubbard A, Cavanagh JB | title = Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons | journal = Neuroscience | volume = 83 | issue = 1 | pages = 295–302 |date=March 1998 | pmid = 9466418 | doi = 10.1016/S0306-4522(97)00388-6}}</ref><ref name="pmid14749382">{{cite journal | author = Moser M, Li Y, Vaupel K, Kretzschmar D, Kluge R, Glynn P, Buettner R | title = Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice | journal = Mol. Cell. Biol. | volume = 24 | issue = 4 | pages = 1667–79 |date=February 2004 | pmid = 14749382 | pmc = 344166 | doi = 10.1128/mcb.24.4.1667-1679.2004}}</ref><ref name="pmid17015841">{{cite journal | author = Gallazzini M, Ferraris JD, Kunin M, Morris RG, Burg MB | title = Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 103 | issue = 41 | pages = 15260–5 |date=October 2006 | pmid = 17015841 | pmc = 1622810 | doi = 10.1073/pnas.0607133103 }}</ref> Loss of NTE activity results in abnormally elevated levels of phosphatidylcholine in brain and impairment of the constitutive secretory pathway in neurons.<ref name="pmid15772346">{{cite journal | author = Mühlig-Versen M, da Cruz AB, Tschäpe JA, Moser M, Büttner R, Athenstaedt K, Glynn P, Kretzschmar D | title = Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila | journal = J. Neurosci. | volume = 25 | issue = 11 | pages = 2865–73 |date=March 2005 | pmid = 15772346 | pmc = 1182176 | doi = 10.1523/JNEUROSCI.5097-04.2005 }}</ref><ref name="pmid19759306">{{cite journal | author = Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P | title = Neuropathy target esterase is required for adult vertebrate axon maintenance | journal = J. Neurosci. | volume = 29 | issue = 37 | pages = 11594–600 |date=September 2009 | pmid = 19759306 | doi = 10.1523/JNEUROSCI.3007-09.2009 }}</ref><ref name="pmid9576844"/>
Neuropathy target esterase is an enzyme with [[phospholipase B]] activity: it sequentially hydrolyses both fatty acids from the major membrane lipid [[phosphatidylcholine]], generating water-soluble glycerophosphocholine.<ref name="pmid16137924">{{cite journal | author = Glynn P | title = Neuropathy target esterase and phospholipid deacylation | journal = Biochim. Biophys. Acta | volume = 1736 | issue = 2 | pages = 87–93 |date=September 2005 | pmid = 16137924 | doi = 10.1016/j.bbalip.2005.08.002 }}</ref><ref name="pmid16731034">{{cite journal |vauthors=Fernández-Murray JP, McMaster CR | title = Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1 | journal = Biochim. Biophys. Acta | volume = 1771 | issue = 3 | pages = 331–6 |date=March 2007 | pmid = 16731034 | doi = 10.1016/j.bbalip.2006.04.004 }}</ref> In [[eukaryotic]] cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In [[mammal]]s, it is particularly abundant in neurons, the [[placenta]], and the kidney.<ref name="pmid12514188">{{cite journal |vauthors=Li Y, Dinsdale D, Glynn P | title = Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells | journal = J. Biol. Chem. | volume = 278 | issue = 10 | pages = 8820–5 |date=March 2003 | pmid = 12514188 | doi = 10.1074/jbc.M210743200 | doi-access = free }}</ref><ref name="pmid15044461">{{cite journal |vauthors=Zaccheo O, Dinsdale D, Meacock PA, Glynn P | title = Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells | journal = J. Biol. Chem. | volume = 279 | issue = 23 | pages = 24024–33 |date=June 2004 | pmid = 15044461 | doi = 10.1074/jbc.M400830200 | doi-access = free }}</ref><ref name="pmid9466418">{{cite journal |vauthors=Glynn P, Holton JL, Nolan CC, Read DJ, Brown L, Hubbard A, Cavanagh JB | title = Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons | journal = Neuroscience | volume = 83 | issue = 1 | pages = 295–302 |date=March 1998 | pmid = 9466418 | doi = 10.1016/S0306-4522(97)00388-6| s2cid = 7075276 }}</ref><ref name="pmid14749382">{{cite journal |vauthors=Moser M, Li Y, Vaupel K, Kretzschmar D, Kluge R, Glynn P, Buettner R | title = Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice | journal = Mol. Cell. Biol. | volume = 24 | issue = 4 | pages = 1667–79 |date=February 2004 | pmid = 14749382 | pmc = 344166 | doi = 10.1128/mcb.24.4.1667-1679.2004}}</ref><ref name="pmid17015841">{{cite journal |vauthors=Gallazzini M, Ferraris JD, Kunin M, Morris RG, Burg MB | title = Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 103 | issue = 41 | pages = 15260–5 |date=October 2006 | pmid = 17015841 | pmc = 1622810 | doi = 10.1073/pnas.0607133103 | bibcode = 2006PNAS..10315260G | doi-access = free }}</ref> Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the [[constitutive secretory pathway]] in neurons.<ref name="pmid9576844"/><ref name="pmid15772346">{{cite journal |vauthors=Mühlig-Versen M, da Cruz AB, Tschäpe JA, Moser M, Büttner R, Athenstaedt K, Glynn P, Kretzschmar D | title = Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila | journal = J. Neurosci. | volume = 25 | issue = 11 | pages = 2865–73 |date=March 2005 | pmid = 15772346 | pmc = 1182176 | doi = 10.1523/JNEUROSCI.5097-04.2005 }}</ref><ref name="pmid19759306">{{cite journal |vauthors=Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P | title = Neuropathy target esterase is required for adult vertebrate axon maintenance | journal = J. Neurosci. | volume = 29 | issue = 37 | pages = 11594–600 |date=September 2009 | pmid = 19759306 | doi = 10.1523/JNEUROSCI.3007-09.2009 | pmc = 3849655 }}</ref>


In [[kidney]], the expression of neuropathy target esterase is regulated by [[NFAT5#Osmotic stress|TonEBP]] as part of [[osmolyte]] production when a [[Arginine vasopressin#Kidney|concentrated urine]] is produced.<ref>{{Cite journal
In the [[kidney]], the expression of neuropathy target esterase is regulated by [[NFAT5#Osmotic stress|TonEBP]] as part of [[osmolyte]] production when the kidney produces concentrated [[urine]].<ref>{{Cite journal
| last1 = Gallazzini | first1 = M.
| last1 = Gallazzini | first1 = M.
| last2 = Burg | first2 = M. B.
| last2 = Burg | first2 = M. B.
| doi = 10.1152/physiol.00009.2009
| doi = 10.1152/physiol.00009.2009
| title = What's New About Osmotic Regulation of Glycerophosphocholine
| title = What's New About Osmotic Regulation of Glycerophosphocholine
| journal = Physiology
| journal = Physiology
| volume = 24
| volume = 24
| issue = 4
| issue = 4
| pages = 245–249
| pages = 245–249
| year = 2009
| year = 2009
| pmid = 19675355
| pmid = 19675355
| pmc =2943332
| pmc =2943332
}}</ref>
}}</ref>


== Clinical significance ==
== Clinical significance ==
Mutations in this gene result in autosomal recessive spastic paraplegia, and the protein is the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents.<ref name="entrez"/>
Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also the target for neurodegeneration induced by [[organophosphorus compound]]s and chemical warfare agents.<ref name="entrez"/>


Recessively-inherited mutations in ''NTE'' that substantially reduce its catalytic activity cause a rare form of [[hereditary spastic paraplegia]] (SPG39), in which distal parts of long spinal [[axons]] degenerate leading to limb weakness and paralysis.<ref name="pmid18313024">{{cite journal | author = Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, Delaney C, Richardson RJ, Albers JW, Matsunami N, Stevens J, Coon H, Leppert M, Fink JK | title = Neuropathy target esterase gene mutations cause motor neuron disease | journal = Am. J. Hum. Genet. | volume = 82 | issue = 3 | pages = 780–5 |date=March 2008 | pmid = 18313024 | pmc = 2427280 | doi = 10.1016/j.ajhg.2007.12.018 }}</ref><ref name="pmid21171093">{{cite journal | author = Rainier S, Albers JW, Dyck PJ, Eldevik OP, Wilcock S, Richardson RJ, Fink JK | title = Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families | journal = Muscle Nerve | volume = 43 | issue = 1 | pages = 19–25 |date=January 2011 | pmid = 21171093 | doi = 10.1002/mus.21777 }}</ref> [[Organophosphate-induced delayed neuropathy]]{{mdash}} a paralysing syndrome with distal degeneration of long axons{{mdash}} results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.<ref name="pmid16042503">{{cite journal | author = Lotti M, Moretto A | title = Organophosphate-induced delayed polyneuropathy | journal = Toxicol Rev | volume = 24 | issue = 1 | pages = 37–49 | year = 2005 | pmid = 16042503 | doi = 10.2165/00139709-200524010-00003| url = }}</ref><ref name="pmid13192490">{{cite journal | author = CAVANAGH JB | title = The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens | journal = J. Neurol. Neurosurg. Psychiatr. | volume = 17 | issue = 3 | pages = 163–72 |date=August 1954 | pmid = 13192490 | pmc = 503178 | doi = 10.1136/jnnp.17.3.163}}</ref><ref name="pmid13877086">{{cite journal | author = CASIDA JE, ETO M, BARON RL | title = Biological activity of a trio-cresyl phosphate metabolite | journal = Nature | volume = 191 | issue = 4796| pages = 1396–7 |date=September 1961 | pmid = 13877086 | doi =10.1038/1911396a0 | url = }}</ref><ref name="pmid4310054">{{cite journal | author = Johnson MK | title = The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase | journal = Biochem. J. | volume = 114 | issue = 4 | pages = 711–7 |date=October 1969 | pmid = 4310054 | pmc = 1184957 | doi = }}</ref><ref name="pmid8043002">{{cite journal | author = Glynn P, Read DJ, Guo R, Wylie S, Johnson MK | title = Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase | journal = Biochem. J. | volume = 301 ( Pt 2) | issue = | pages = 551–6 |date=July 1994 | pmid = 8043002 | pmc = 1137116 | doi = }}</ref><ref name="pmid20188121">{{cite journal | author = Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P | title = Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase | journal = Toxicol. Appl. Pharmacol. | volume = 245 | issue = 1 | pages = 108–15 |date=May 2010 | pmid = 20188121 | doi = 10.1016/j.taap.2010.02.010 }}</ref>
Recessively-inherited mutations in ''NTE'' that substantially reduce its catalytic activity cause a rare form of [[hereditary spastic paraplegia]] (SPG39), in which distal parts of long spinal [[axons]] degenerate leading to limb weakness and paralysis.<ref name="pmid18313024">{{cite journal |vauthors=Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, Delaney C, Richardson RJ, Albers JW, Matsunami N, Stevens J, Coon H, Leppert M, Fink JK | title = Neuropathy target esterase gene mutations cause motor neuron disease | journal = Am. J. Hum. Genet. | volume = 82 | issue = 3 | pages = 780–5 |date=March 2008 | pmid = 18313024 | pmc = 2427280 | doi = 10.1016/j.ajhg.2007.12.018 }}</ref><ref name="pmid21171093">{{cite journal |vauthors=Rainier S, Albers JW, Dyck PJ, Eldevik OP, Wilcock S, Richardson RJ, Fink JK | title = Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families | journal = Muscle Nerve | volume = 43 | issue = 1 | pages = 19–25 |date=January 2011 | pmid = 21171093 | doi = 10.1002/mus.21777 | hdl = 2027.42/78477 | s2cid = 1621142 | hdl-access = free }}</ref> [[Organophosphate-induced delayed neuropathy]]{{mdash}} a paralysing syndrome with distal degeneration of long axons{{mdash}} results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.<ref name="pmid16042503">{{cite journal |vauthors=Lotti M, Moretto A | title = Organophosphate-induced delayed polyneuropathy | journal = Toxicol Rev | volume = 24 | issue = 1 | pages = 37–49 | year = 2005 | pmid = 16042503 | doi = 10.2165/00139709-200524010-00003| s2cid = 29313644 }}</ref><ref name="pmid13192490">{{cite journal | author = CAVANAGH JB | title = The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens | journal = J. Neurol. Neurosurg. Psychiatry | volume = 17 | issue = 3 | pages = 163–72 |date=August 1954 | pmid = 13192490 | pmc = 503178 | doi = 10.1136/jnnp.17.3.163}}</ref><ref name="pmid13877086">{{cite journal |vauthors=CASIDA JE, ETO M, BARON RL | title = Biological activity of a trio-cresyl phosphate metabolite | journal = Nature | volume = 191 | issue = 4796| pages = 1396–7 |date=September 1961 | pmid = 13877086 | doi =10.1038/1911396a0 | bibcode = 1961Natur.191.1396C | s2cid = 4195141 }}</ref><ref name="pmid4310054">{{cite journal | author = Johnson MK | title = The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase | journal = Biochem. J. | volume = 114 | issue = 4 | pages = 711–7 |date=October 1969 | pmid = 4310054 | pmc = 1184957 | doi = 10.1042/bj1140711}}</ref><ref name="pmid8043002">{{cite journal |vauthors=Glynn P, Read DJ, Guo R, Wylie S, Johnson MK | title = Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase | journal = Biochem. J. | volume = 301 ( Pt 2) | issue = 2| pages = 551–6 |date=July 1994 | pmid = 8043002 | pmc = 1137116 | doi = 10.1042/bj3010551}}</ref><ref name="pmid20188121">{{cite journal |vauthors=Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P | title = Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase | journal = Toxicol. Appl. Pharmacol. | volume = 245 | issue = 1 | pages = 108–15 |date=May 2010 | pmid = 20188121 | doi = 10.1016/j.taap.2010.02.010 }}</ref>


==References==
==References==
Line 31: Line 33:
==Further reading==
==Further reading==
{{refbegin |20em}}
{{refbegin |20em}}
*{{cite journal | author=Glynn P |title=Neural development and neurodegeneration: two faces of neuropathy target esterase. |journal=Prog. Neurobiol. |volume=61 |issue= 1 |pages= 61–74 |year= 2000 |pmid= 10759065 |doi=10.1016/S0301-0082(99)00043-X }}
* {{cite journal | author=Glynn P |title=Neural development and neurodegeneration: two faces of neuropathy target esterase. |journal=Prog. Neurobiol. |volume=61 |issue= 1 |pages= 61–74 |year= 2000 |pmid= 10759065 |doi=10.1016/S0301-0082(99)00043-X |s2cid=20322620 }}
*{{cite journal | author=Maroni M, Bleecker ML |title=Neuropathy target esterase in human lymphocytes and platelets. |journal=Journal of applied toxicology : JAT |volume=6 |issue= 1 |pages= 1–7 |year= 1986 |pmid= 3958422 |doi=10.1002/jat.2550060102 }}
* {{cite journal |vauthors=Maroni M, Bleecker ML |title=Neuropathy target esterase in human lymphocytes and platelets. |journal=Journal of Applied Toxicology |volume=6 |issue= 1 |pages= 1–7 |year= 1986 |pmid= 3958422 |doi=10.1002/jat.2550060102 |s2cid=21763818 }}
*{{cite journal | author=Bertoncin D, Russolo A, Caroldi S, Lotti M |title=Neuropathy target esterase in human lymphocytes. |journal=Arch. Environ. Health |volume=40 |issue= 3 |pages= 139–44 |year= 1985 |pmid= 4026382 |doi= 10.1080/00039896.1985.10545905}}
* {{cite journal |vauthors=Bertoncin D, Russolo A, Caroldi S, Lotti M |title=Neuropathy target esterase in human lymphocytes. |journal=Arch. Environ. Health |volume=40 |issue= 3 |pages= 139–44 |year= 1985 |pmid= 4026382 |doi= 10.1080/00039896.1985.10545905}}
*{{cite journal | author=Gurba PE, Richardson RJ |title=Partial characterization of neurotoxic esterase of human placenta. |journal=Toxicol. Lett. |volume=15 |issue= 1 |pages= 13–7 |year= 1983 |pmid= 6836585 |doi=10.1016/0378-4274(83)90162-5 }}
* {{cite journal |vauthors=Gurba PE, Richardson RJ |title=Partial characterization of neurotoxic esterase of human placenta. |journal=Toxicol. Lett. |volume=15 |issue= 1 |pages= 13–7 |year= 1983 |pmid= 6836585 |doi=10.1016/0378-4274(83)90162-5 |url=https://deepblue.lib.umich.edu/bitstream/2027.42/25337/1/0000783.pdf |hdl=2027.42/25337 |hdl-access=free }}
*{{cite journal | author=van Tienhoven M, Atkins J, Li Y, Glynn P |title=Human neuropathy target esterase catalyzes hydrolysis of membrane lipids. |journal=J. Biol. Chem. |volume=277 |issue= 23 |pages= 20942–8 |year= 2002 |pmid= 11927584 |doi= 10.1074/jbc.M200330200 }}
* {{cite journal |vauthors=van Tienhoven M, Atkins J, Li Y, Glynn P |title=Human neuropathy target esterase catalyzes hydrolysis of membrane lipids. |journal=J. Biol. Chem. |volume=277 |issue= 23 |pages= 20942–8 |year= 2002 |pmid= 11927584 |doi= 10.1074/jbc.M200330200 |doi-access= free }}
*{{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 |name-list-format=vanc | author2=Feingold EA | author3=Grouse LH | display-authors=3 | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD }}
* {{cite journal | author=Strausberg RL |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899 | pmc=139241 | author2=Feingold EA | author3=Grouse LH | last4=Derge | first4=JG | last5=Klausner | first5=RD | last6=Collins | first6=FS | last7=Wagner | first7=L | last8=Shenmen | first8=CM | last9=Schuler | first9=GD |bibcode=2002PNAS...9916899M |doi-access=free }}
*{{cite journal | author=Li Y, Dinsdale D, Glynn P |title=Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells |journal=J. Biol. Chem. |volume=278 |issue= 10 |pages= 8820–5 |year= 2003 |pmid= 12514188 |doi= 10.1074/jbc.M210743200 }}
* {{cite journal |vauthors=Li Y, Dinsdale D, Glynn P |title=Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells |journal=J. Biol. Chem. |volume=278 |issue= 10 |pages= 8820–5 |year= 2003 |pmid= 12514188 |doi= 10.1074/jbc.M210743200 |doi-access= free }}
*{{cite journal | author=Winrow CJ |title=Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity |journal=Nat. Genet. |volume=33 |issue= 4 |pages= 477–85 |year= 2003 |pmid= 12640454 |doi= 10.1038/ng1131 |name-list-format=vanc | author2=Hemming ML | author3=Allen DM | display-authors=3 | last4=Quistad | first4=Gary B. | last5=Casida | first5=John E. | last6=Barlow | first6=Carrolee }}
* {{cite journal | author=Winrow CJ |title=Loss of neuropathy target esterase in mice links organophosphate exposure to hyperactivity |journal=Nat. Genet. |volume=33 |issue= 4 |pages= 477–85 |year= 2003 |pmid= 12640454 |doi= 10.1038/ng1131 | author2=Hemming ML | author3=Allen DM | last4=Quistad | first4=Gary B. | last5=Casida | first5=John E. | last6=Barlow | first6=Carrolee | doi-access=free }}
*{{cite journal | author=Zaccheo O, Dinsdale D, Meacock PA, Glynn P |title=Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells |journal=J. Biol. Chem. |volume=279 |issue= 23 |pages= 24024–33 |year= 2004 |pmid= 15044461 |doi= 10.1074/jbc.M400830200 }}
* {{cite journal |vauthors=Zaccheo O, Dinsdale D, Meacock PA, Glynn P |title=Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells |journal=J. Biol. Chem. |volume=279 |issue= 23 |pages= 24024–33 |year= 2004 |pmid= 15044461 |doi= 10.1074/jbc.M400830200 |doi-access= free }}
*{{cite journal | author=Beausoleil SA |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 |name-list-format=vanc | author2=Jedrychowski M | author3=Schwartz D | display-authors=3 | last4=Elias | first4=JE | last5=Villén | first5=J | last6=Li | first6=J | last7=Cohn | first7=MA | last8=Cantley | first8=LC | last9=Gygi | first9=SP }}
* {{cite journal | author=Beausoleil SA |title=Large-scale characterization of HeLa cell nuclear phosphoproteins |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=101 |issue= 33 |pages= 12130–5 |year= 2004 |pmid= 15302935 |doi= 10.1073/pnas.0404720101 | pmc=514446 | author2=Jedrychowski M | author3=Schwartz D | last4=Elias | first4=JE | last5=Villén | first5=J | last6=Li | first6=J | last7=Cohn | first7=MA | last8=Cantley | first8=LC | last9=Gygi | first9=SP |bibcode=2004PNAS..10112130B |doi-access=free }}
*{{cite journal | author=Chang PA |title=Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line |journal=Mol. Cell. Biochem. |volume=272 |issue= 1–2 |pages= 47–54 |year= 2005 |pmid= 16010971 |doi=10.1007/s11010-005-6753-2 |name-list-format=vanc | author2=Wu YJ | author3=Chen R | display-authors=3 | last4=Li | first4=Ming | last5=Li | first5=Wei | last6=Qin | first6=Qi-Lian }}
* {{cite journal | author=Chang PA |title=Inhibition of neuropathy target esterase expressing by antisense RNA does not affect neural differentiation in human neuroblastoma (SK-N-SH) cell line |journal=Mol. Cell. Biochem. |volume=272 |issue= 1–2 |pages= 47–54 |year= 2005 |pmid= 16010971 |doi=10.1007/s11010-005-6753-2 | author2=Wu YJ | author3=Chen R | last4=Li | first4=Ming | last5=Li | first5=Wei | last6=Qin | first6=Qi-Lian |s2cid=20498617 }}
*{{cite journal | author=Chang PA, Chen R, Wu YJ |title=Reduction of neuropathy target esterase does not affect neuronal differentiation, but moderate expression induces neuronal differentiation in human neuroblastoma (SK-N-SH) cell line |journal=Brain Res. Mol. Brain Res. |volume=141 |issue= 1 |pages= 30–8 |year= 2006 |pmid= 16122834 |doi= 10.1016/j.molbrainres.2005.07.012 }}
* {{cite journal |vauthors=Chang PA, Chen R, Wu YJ |title=Reduction of neuropathy target esterase does not affect neuronal differentiation, but moderate expression induces neuronal differentiation in human neuroblastoma (SK-N-SH) cell line |journal=Brain Res. Mol. Brain Res. |volume=141 |issue= 1 |pages= 30–8 |year= 2006 |pmid= 16122834 |doi= 10.1016/j.molbrainres.2005.07.012 |s2cid=22182434 }}
*{{cite journal | author=Kimura K |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 | pmc=1356129 |name-list-format=vanc | author2=Wakamatsu A | author3=Suzuki Y | display-authors=3 | last4=Ota | first4=T | last5=Nishikawa | first5=T | last6=Yamashita | first6=R | last7=Yamamoto | first7=J | last8=Sekine | first8=M | last9=Tsuritani | first9=K }}
* {{cite journal | author=Kimura K |title=Diversification of transcriptional modulation: large-scale identification and characterization of putative alternative promoters of human genes |journal=Genome Res. |volume=16 |issue= 1 |pages= 55–65 |year= 2006 |pmid= 16344560 |doi= 10.1101/gr.4039406 | pmc=1356129 | author2=Wakamatsu A | author3=Suzuki Y | last4=Ota | first4=T | last5=Nishikawa | first5=T | last6=Yamashita | first6=R | last7=Yamamoto | first7=J | last8=Sekine | first8=M | last9=Tsuritani | first9=K }}
*{{cite journal | author=Chang PA, Liu ChY, Chen R, Wu YJ |title=Effect of over-expression of neuropathy target esterase on mammalian cell proliferation |journal=Cell Prolif. |volume=39 |issue= 5 |pages= 429–40 |year= 2006 |pmid= 16987144 |doi= 10.1111/j.1365-2184.2006.00399.x }}
* {{cite journal |author1=Chang PA |author2=Liu ChY |author3=Chen R |author4=Wu YJ |title=Effect of over-expression of neuropathy target esterase on mammalian cell proliferation |journal=Cell Prolif. |volume=39 |issue= 5 |pages= 429–40 |year= 2006 |pmid= 16987144 |doi= 10.1111/j.1365-2184.2006.00399.x |pmc=6496609 }}
*{{cite journal | author=Chen R |title=Down-regulation of neuropathy target esterase by protein kinase C activation with PMA stimulation |journal=Mol. Cell. Biochem. |volume=302 |issue= 1–2 |pages= 179–85 |year= 2007 |pmid= 17385009 |doi= 10.1007/s11010-007-9439-0 |name-list-format=vanc | author2=Chang PA | author3=Long DX | display-authors=3 | last4=Yang | first4=Lin | last5=Wu | first5=Yi-Jun }}
* {{cite journal | author=Chen R |title=Down-regulation of neuropathy target esterase by protein kinase C activation with PMA stimulation |journal=Mol. Cell. Biochem. |volume=302 |issue= 1–2 |pages= 179–85 |year= 2007 |pmid= 17385009 |doi= 10.1007/s11010-007-9439-0 | author2=Chang PA | author3=Long DX | last4=Yang | first4=Lin | last5=Wu | first5=Yi-Jun |s2cid=1235494 }}
{{refend}}
{{refend}}

{{Esterases}}
{{Enzymes}}
{{Portal bar|Biology|border=no}}


{{NLM content}}
{{NLM content}}

Latest revision as of 09:48, 27 January 2024

PNPLA6
Identifiers
AliasesPNPLA6, BNHS, NTE, NTEMND, SPG39, iPLA2delta, sws, LNMS, OMCS, patatin like phospholipase domain containing 6
External IDsOMIM: 603197 MGI: 1354723 HomoloGene: 21333 GeneCards: PNPLA6
Orthologs
SpeciesHumanMouse
Entrez

10908

50767

Ensembl

ENSG00000032444

ENSMUSG00000004565

UniProt

Q8IY17

Q3TRM4

RefSeq (mRNA)

NM_006702
NM_001166111
NM_001166112
NM_001166113
NM_001166114

RefSeq (protein)

NP_001159583
NP_001159584
NP_001159585
NP_001159586
NP_006693

Location (UCSC)Chr 19: 7.53 – 7.56 MbChr 8: 3.57 – 3.59 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse

Neuropathy target esterase, also known as patatin-like phospholipase domain-containing protein 6 (PNPLA6), is an esterase enzyme that in humans is encoded by the PNPLA6 gene.[5][6][7][8]

Neuropathy target esterase is a phospholipase that deacetylates intracellular phosphatidylcholine to produce glycerophosphocholine. It is thought to function in neurite outgrowth and process elongation during neuronal differentiation. The protein is anchored to the cytoplasmic face of the endoplasmic reticulum in both neurons and non-neuronal cells.[8]

Function[edit]

Neuropathy target esterase is an enzyme with phospholipase B activity: it sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine, generating water-soluble glycerophosphocholine.[9][10] In eukaryotic cells, NTE is anchored to the cytoplasmic face of the endoplasmic reticulum membrane. In mammals, it is particularly abundant in neurons, the placenta, and the kidney.[11][12][13][14][15] Loss of NTE activity results in abnormally-elevated levels of phosphatidylcholine in the brain and impairment of the constitutive secretory pathway in neurons.[5][16][17]

In the kidney, the expression of neuropathy target esterase is regulated by TonEBP as part of osmolyte production when the kidney produces concentrated urine.[18]

Clinical significance[edit]

Mutations in this gene result in autosomal-recessive spastic paraplegia. The protein is also the target for neurodegeneration induced by organophosphorus compounds and chemical warfare agents.[8]

Recessively-inherited mutations in NTE that substantially reduce its catalytic activity cause a rare form of hereditary spastic paraplegia (SPG39), in which distal parts of long spinal axons degenerate leading to limb weakness and paralysis.[19][20] Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.[21][22][23][24][25][26]

References[edit]

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000032444 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000004565 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ a b Lush MJ, Li Y, Read DJ, Willis AC, Glynn P (Aug 1998). "Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man". Biochem J. 332. ( Pt 1) (Pt 1): 1–4. doi:10.1042/bj3320001. PMC 1219444. PMID 9576844.
  6. ^ Wilson PA, Gardner SD, Lambie NM, Commans SA, Crowther DJ (Aug 2006). "Characterization of the human patatin-like phospholipase family". J Lipid Res. 47 (9): 1940–9. doi:10.1194/jlr.M600185-JLR200. PMID 16799181.
  7. ^ Kienesberger PC, Oberer M, Lass A, Zechner R (Apr 2009). "Mammalian patatin domain containing proteins: a family with diverse lipolytic activities involved in multiple biological functions". J Lipid Res. 50 Suppl (Supplement): S63–8. doi:10.1194/jlr.R800082-JLR200. PMC 2674697. PMID 19029121.
  8. ^ a b c "Entrez Gene: PNPLA6 patatin-like phospholipase domain containing 6".
  9. ^ Glynn P (September 2005). "Neuropathy target esterase and phospholipid deacylation". Biochim. Biophys. Acta. 1736 (2): 87–93. doi:10.1016/j.bbalip.2005.08.002. PMID 16137924.
  10. ^ Fernández-Murray JP, McMaster CR (March 2007). "Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1". Biochim. Biophys. Acta. 1771 (3): 331–6. doi:10.1016/j.bbalip.2006.04.004. PMID 16731034.
  11. ^ Li Y, Dinsdale D, Glynn P (March 2003). "Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in Mammalian cells". J. Biol. Chem. 278 (10): 8820–5. doi:10.1074/jbc.M210743200. PMID 12514188.
  12. ^ Zaccheo O, Dinsdale D, Meacock PA, Glynn P (June 2004). "Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells". J. Biol. Chem. 279 (23): 24024–33. doi:10.1074/jbc.M400830200. PMID 15044461.
  13. ^ Glynn P, Holton JL, Nolan CC, Read DJ, Brown L, Hubbard A, et al. (March 1998). "Neuropathy target esterase: immunolocalization to neuronal cell bodies and axons". Neuroscience. 83 (1): 295–302. doi:10.1016/S0306-4522(97)00388-6. PMID 9466418. S2CID 7075276.
  14. ^ Moser M, Li Y, Vaupel K, Kretzschmar D, Kluge R, Glynn P, et al. (February 2004). "Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice". Mol. Cell. Biol. 24 (4): 1667–79. doi:10.1128/mcb.24.4.1667-1679.2004. PMC 344166. PMID 14749382.
  15. ^ Gallazzini M, Ferraris JD, Kunin M, Morris RG, Burg MB (October 2006). "Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl". Proc. Natl. Acad. Sci. U.S.A. 103 (41): 15260–5. Bibcode:2006PNAS..10315260G. doi:10.1073/pnas.0607133103. PMC 1622810. PMID 17015841.
  16. ^ Mühlig-Versen M, da Cruz AB, Tschäpe JA, Moser M, Büttner R, Athenstaedt K, et al. (March 2005). "Loss of Swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila". J. Neurosci. 25 (11): 2865–73. doi:10.1523/JNEUROSCI.5097-04.2005. PMC 1182176. PMID 15772346.
  17. ^ Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (September 2009). "Neuropathy target esterase is required for adult vertebrate axon maintenance". J. Neurosci. 29 (37): 11594–600. doi:10.1523/JNEUROSCI.3007-09.2009. PMC 3849655. PMID 19759306.
  18. ^ Gallazzini M, Burg MB (2009). "What's New About Osmotic Regulation of Glycerophosphocholine". Physiology. 24 (4): 245–249. doi:10.1152/physiol.00009.2009. PMC 2943332. PMID 19675355.
  19. ^ Rainier S, Bui M, Mark E, Thomas D, Tokarz D, Ming L, et al. (March 2008). "Neuropathy target esterase gene mutations cause motor neuron disease". Am. J. Hum. Genet. 82 (3): 780–5. doi:10.1016/j.ajhg.2007.12.018. PMC 2427280. PMID 18313024.
  20. ^ Rainier S, Albers JW, Dyck PJ, Eldevik OP, Wilcock S, Richardson RJ, et al. (January 2011). "Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families". Muscle Nerve. 43 (1): 19–25. doi:10.1002/mus.21777. hdl:2027.42/78477. PMID 21171093. S2CID 1621142.
  21. ^ Lotti M, Moretto A (2005). "Organophosphate-induced delayed polyneuropathy". Toxicol Rev. 24 (1): 37–49. doi:10.2165/00139709-200524010-00003. PMID 16042503. S2CID 29313644.
  22. ^ CAVANAGH JB (August 1954). "The toxic effects of triortho-cresyl phosphate on the nervous system; an experimental study in hens". J. Neurol. Neurosurg. Psychiatry. 17 (3): 163–72. doi:10.1136/jnnp.17.3.163. PMC 503178. PMID 13192490.
  23. ^ CASIDA JE, ETO M, BARON RL (September 1961). "Biological activity of a trio-cresyl phosphate metabolite". Nature. 191 (4796): 1396–7. Bibcode:1961Natur.191.1396C. doi:10.1038/1911396a0. PMID 13877086. S2CID 4195141.
  24. ^ Johnson MK (October 1969). "The delayed neurotoxic effect of some organophosphorus compounds. Identification of the phosphorylation site as an esterase". Biochem. J. 114 (4): 711–7. doi:10.1042/bj1140711. PMC 1184957. PMID 4310054.
  25. ^ Glynn P, Read DJ, Guo R, Wylie S, Johnson MK (July 1994). "Synthesis and characterization of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase". Biochem. J. 301 ( Pt 2) (2): 551–6. doi:10.1042/bj3010551. PMC 1137116. PMID 8043002.
  26. ^ Read DJ, Li Y, Chao MV, Cavanagh JB, Glynn P (May 2010). "Organophosphates induce distal axonal damage, but not brain oedema, by inactivating neuropathy target esterase". Toxicol. Appl. Pharmacol. 245 (1): 108–15. doi:10.1016/j.taap.2010.02.010. PMID 20188121.

Further reading[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Retrieved from "https://en.wikipedia.org/w/index.php?title=Neuropathy_target_esterase&oldid=1199548947"