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{{Merge from|PNPLA6|discuss=Neuropathy target esterase#Merge discussion|date=May 2011}}
'''Neuropathy target esterase''' (NTE/[[PNPLA6]]) 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=Glynn> Glynn, P (2005) Neuropathy target esterase and phospholipid deacylation. ''Biochimica et Biophysica Acta'' 1736, 87-93. PMID 16137924</ref><ref name=Murray>Fernandez-Murray, JP, McMaster, CR (2007) Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1. ''Biochimica et Biophysica Acta'' 1771, 331-336. PMID 16731034</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=Li>Li, Y, Dinsdale, D, Glynn, P (2003) Protein domains, catalytic activity and subcellular distribution of neuropathy target esterase in mammalian cells. ''J. Biol. Chem''. 278, 8820-8825. PMID 12514188</ref><ref name=Zaccheo>Zaccheo, O, Dinsdale, D, Meacock, PA, Glynn, P (2004). Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells. ''J. Biol. Chem''. 279, 24024-24033. PMID 15044461</ref><ref name=Holton>Glynn, P, Holton, JL, Nolan, CC, Read, DJ, Brown, L, Hubbard, A, Cavanagh, JB (1998) Neuropathy target esterase: immunolocalisation to neuronal cell bodies and axons. ''Neuroscience'' 83, 295-302. PMID 9466418</ref><ref name=Moser> Moser, M, Li, Y, Vaupel, K, Kretzschmar, D, Kluge, R, Glynn, P, Buettner, R (2004). Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice. ''Mol. Cell. Biol''. 24, 1667-1679. PMID 14749382</ref><ref name=Burg>Gallazzini, M, Ferraris, JD, Kunin, M, Morris, RG, Burg, MB (2006) Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl. ''Proc. Natl. Acad. Sci. (USA)'' 103, 15260-15265. PMID 17015841</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=MuhligVersen>Muhlig-Versen, M, da Cruz, AB, Tschape, J-A, Moser, M, Buttner, R, Athenstaedt, K, Glynn, P, Kretzschmar, D (2005) Loss of swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult ''Drosophila''. ''J. Neuroscience'' 25, 2865-2873. PMID 15772346</ref><ref name=Read>Read, DJ, Li, Y, Chao, MV, Cavanagh, JB, Glynn, P (2009) Neuropathy target esterase is required for adult vertebrate axon maintenance. ''J. Neuroscience'' 29, 11594-11600. PMID 19759306</ref> The human ''NTE'' gene is on chromosome 19p13.3.<ref name=Lush>Lush, MJ, Li, Y, Read, DJ, Willis, AC, Glynn, P (1998). Neuropathy target esterase and a homologous ''Drosophila'' neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. ''Biochem. J''. 332, 1-4. PMID 9576844</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=Rainier>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 (2008) Neuropathy target esterase gene mutations cause motor neuron disease. ''Amer. J. Hum. Genet''. 82, 780-785. PMID 18313024</ref><ref name=Fink>Rainier, S, Albers, JW, Dyck, PJ, Eldevik, OP, Wilcock, S, Richardson, RJ, Fink, JK (2011) Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families. ''Muscle Nerve'' 43, 19-25. PMID 21171093</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=Lotti>Lotti, M, Moretto, A (2005) Organophosphate-induced delayed polyneuropathy. ''Toxicol. Rev''. 24, 37-49. PMID 16042503</ref><ref name=Cavanagh>Cavanagh, JB (1954) The toxic effects of tri-ortho-cresyl phosphate on the nervous system: an experimental study in hens. ''J. Neurol. Neurosurg. Psychiatry'' 17, 163-172. PMID 13192490</ref><ref name=Casida>Casida JE, Eto, M Baron, RL (1961) Biological activity of a tri-o-cresyl phosphate metabolite. ''Nature'' 191, 1396-1397. PMID 13877086</ref><ref name=Johnson>Johnson, MK (1969) The delayed neurotoxic action of some organophosphorus compounds. Identification of the phosphorylation site as an esterase. ''Biochem. J''. 114, 711-717. PMID 4310054</ref><ref name=Guo>Glynn, P, Read, DJ, Guo, R, Wylie, S, Johnson, MK (1994) Synthesis and characterisation of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase. ''Biochem. J''. 301, 551-556. PMID 8043002</ref><ref name=Chao>Read, DJ, Li, Y, Chao, MV, Cavanagh, JB, Glynn, P (2010) Organophosphates induce distal axonal damage, but not brain oedema, by inhibiting neuropathy target esterase. ''Toxicol. Appl. Pharmacol''. 245, 108-115. PMID 20188121</ref>
'''Neuropathy target esterase''' (NTE/[[PNPLA6]]) 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=Glynn> Glynn, P (2005) Neuropathy target esterase and phospholipid deacylation. ''Biochimica et Biophysica Acta'' 1736, 87-93. PMID 16137924</ref><ref name=Murray>Fernandez-Murray, JP, McMaster, CR (2007) Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1. ''Biochimica et Biophysica Acta'' 1771, 331-336. PMID 16731034</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=Li>Li, Y, Dinsdale, D, Glynn, P (2003) Protein domains, catalytic activity and subcellular distribution of neuropathy target esterase in mammalian cells. ''J. Biol. Chem''. 278, 8820-8825. PMID 12514188</ref><ref name=Zaccheo>Zaccheo, O, Dinsdale, D, Meacock, PA, Glynn, P (2004). Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells. ''J. Biol. Chem''. 279, 24024-24033. PMID 15044461</ref><ref name=Holton>Glynn, P, Holton, JL, Nolan, CC, Read, DJ, Brown, L, Hubbard, A, Cavanagh, JB (1998) Neuropathy target esterase: immunolocalisation to neuronal cell bodies and axons. ''Neuroscience'' 83, 295-302. PMID 9466418</ref><ref name=Moser> Moser, M, Li, Y, Vaupel, K, Kretzschmar, D, Kluge, R, Glynn, P, Buettner, R (2004). Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice. ''Mol. Cell. Biol''. 24, 1667-1679. PMID 14749382</ref><ref name=Burg>Gallazzini, M, Ferraris, JD, Kunin, M, Morris, RG, Burg, MB (2006) Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl. ''Proc. Natl. Acad. Sci. (USA)'' 103, 15260-15265. PMID 17015841</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=MuhligVersen>Muhlig-Versen, M, da Cruz, AB, Tschape, J-A, Moser, M, Buttner, R, Athenstaedt, K, Glynn, P, Kretzschmar, D (2005) Loss of swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult ''Drosophila''. ''J. Neuroscience'' 25, 2865-2873. PMID 15772346</ref><ref name=Read>Read, DJ, Li, Y, Chao, MV, Cavanagh, JB, Glynn, P (2009) Neuropathy target esterase is required for adult vertebrate axon maintenance. ''J. Neuroscience'' 29, 11594-11600. PMID 19759306</ref> The human ''NTE'' gene is on chromosome 19p13.3.<ref name=Lush>Lush, MJ, Li, Y, Read, DJ, Willis, AC, Glynn, P (1998). Neuropathy target esterase and a homologous ''Drosophila'' neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. ''Biochem. J''. 332, 1-4. PMID 9576844</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=Rainier>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 (2008) Neuropathy target esterase gene mutations cause motor neuron disease. ''Amer. J. Hum. Genet''. 82, 780-785. PMID 18313024</ref><ref name=Fink>Rainier, S, Albers, JW, Dyck, PJ, Eldevik, OP, Wilcock, S, Richardson, RJ, Fink, JK (2011) Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families. ''Muscle Nerve'' 43, 19-25. PMID 21171093</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=Lotti>Lotti, M, Moretto, A (2005) Organophosphate-induced delayed polyneuropathy. ''Toxicol. Rev''. 24, 37-49. PMID 16042503</ref><ref name=Cavanagh>Cavanagh, JB (1954) The toxic effects of tri-ortho-cresyl phosphate on the nervous system: an experimental study in hens. ''J. Neurol. Neurosurg. Psychiatry'' 17, 163-172. PMID 13192490</ref><ref name=Casida>Casida JE, Eto, M Baron, RL (1961) Biological activity of a tri-o-cresyl phosphate metabolite. ''Nature'' 191, 1396-1397. PMID 13877086</ref><ref name=Johnson>Johnson, MK (1969) The delayed neurotoxic action of some organophosphorus compounds. Identification of the phosphorylation site as an esterase. ''Biochem. J''. 114, 711-717. PMID 4310054</ref><ref name=Guo>Glynn, P, Read, DJ, Guo, R, Wylie, S, Johnson, MK (1994) Synthesis and characterisation of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase. ''Biochem. J''. 301, 551-556. PMID 8043002</ref><ref name=Chao>Read, DJ, Li, Y, Chao, MV, Cavanagh, JB, Glynn, P (2010) Organophosphates induce distal axonal damage, but not brain oedema, by inhibiting neuropathy target esterase. ''Toxicol. Appl. Pharmacol''. 245, 108-115. PMID 20188121</ref>


Revision as of 05:03, 20 May 2011

Neuropathy target esterase (NTE/PNPLA6) is an enzyme with phospholipase B activity: It sequentially hydrolyses both fatty acids from the major membrane lipid phosphatidylcholine, which generates water-soluble glycerophosphocholine.[1][2] 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.[3][4][5][6][7] Loss of NTE activity results in abnormally elevated levels of phosphatidylcholine in brain and impairment of the constitutive secretory pathway in neurons.[8][9] The human NTE gene is on chromosome 19p13.3.[10] 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.[11][12] Organophosphate-induced delayed neuropathy— a paralysing syndrome with distal degeneration of long axons— results from poisoning with neuropathic organophosphorus compounds that irreversibly inhibit NTE.[13][14][15][16][17][18]

References

  1. ^ Glynn, P (2005) Neuropathy target esterase and phospholipid deacylation. Biochimica et Biophysica Acta 1736, 87-93. PMID 16137924
  2. ^ Fernandez-Murray, JP, McMaster, CR (2007) Phosphatidylcholine synthesis and its catabolism by yeast neuropathy target esterase 1. Biochimica et Biophysica Acta 1771, 331-336. PMID 16731034
  3. ^ Li, Y, Dinsdale, D, Glynn, P (2003) Protein domains, catalytic activity and subcellular distribution of neuropathy target esterase in mammalian cells. J. Biol. Chem. 278, 8820-8825. PMID 12514188
  4. ^ Zaccheo, O, Dinsdale, D, Meacock, PA, Glynn, P (2004). Neuropathy target esterase and its yeast homologue degrade phosphatidylcholine to glycerophosphocholine in living cells. J. Biol. Chem. 279, 24024-24033. PMID 15044461
  5. ^ Glynn, P, Holton, JL, Nolan, CC, Read, DJ, Brown, L, Hubbard, A, Cavanagh, JB (1998) Neuropathy target esterase: immunolocalisation to neuronal cell bodies and axons. Neuroscience 83, 295-302. PMID 9466418
  6. ^ Moser, M, Li, Y, Vaupel, K, Kretzschmar, D, Kluge, R, Glynn, P, Buettner, R (2004). Placental failure and impaired vasculogenesis result in embryonic lethality for neuropathy target esterase-deficient mice. Mol. Cell. Biol. 24, 1667-1679. PMID 14749382
  7. ^ Gallazzini, M, Ferraris, JD, Kunin, M, Morris, RG, Burg, MB (2006) Neuropathy target esterase catalyzes osmoprotective renal synthesis of glycerophosphocholine in response to high NaCl. Proc. Natl. Acad. Sci. (USA) 103, 15260-15265. PMID 17015841
  8. ^ Muhlig-Versen, M, da Cruz, AB, Tschape, J-A, Moser, M, Buttner, R, Athenstaedt, K, Glynn, P, Kretzschmar, D (2005) Loss of swiss cheese/neuropathy target esterase activity causes disruption of phosphatidylcholine homeostasis and neuronal and glial death in adult Drosophila. J. Neuroscience 25, 2865-2873. PMID 15772346
  9. ^ Read, DJ, Li, Y, Chao, MV, Cavanagh, JB, Glynn, P (2009) Neuropathy target esterase is required for adult vertebrate axon maintenance. J. Neuroscience 29, 11594-11600. PMID 19759306
  10. ^ Lush, MJ, Li, Y, Read, DJ, Willis, AC, Glynn, P (1998). Neuropathy target esterase and a homologous Drosophila neurodegeneration-associated mutant protein contain a novel domain conserved from bacteria to man. Biochem. J. 332, 1-4. PMID 9576844
  11. ^ 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 (2008) Neuropathy target esterase gene mutations cause motor neuron disease. Amer. J. Hum. Genet. 82, 780-785. PMID 18313024
  12. ^ Rainier, S, Albers, JW, Dyck, PJ, Eldevik, OP, Wilcock, S, Richardson, RJ, Fink, JK (2011) Motor neuron disease due to neuropathy target esterase gene mutation: clinical features of the index families. Muscle Nerve 43, 19-25. PMID 21171093
  13. ^ Lotti, M, Moretto, A (2005) Organophosphate-induced delayed polyneuropathy. Toxicol. Rev. 24, 37-49. PMID 16042503
  14. ^ Cavanagh, JB (1954) The toxic effects of tri-ortho-cresyl phosphate on the nervous system: an experimental study in hens. J. Neurol. Neurosurg. Psychiatry 17, 163-172. PMID 13192490
  15. ^ Casida JE, Eto, M Baron, RL (1961) Biological activity of a tri-o-cresyl phosphate metabolite. Nature 191, 1396-1397. PMID 13877086
  16. ^ Johnson, MK (1969) The delayed neurotoxic action of some organophosphorus compounds. Identification of the phosphorylation site as an esterase. Biochem. J. 114, 711-717. PMID 4310054
  17. ^ Glynn, P, Read, DJ, Guo, R, Wylie, S, Johnson, MK (1994) Synthesis and characterisation of a biotinylated organophosphorus ester for detection and affinity purification of a brain serine esterase: neuropathy target esterase. Biochem. J. 301, 551-556. PMID 8043002
  18. ^ Read, DJ, Li, Y, Chao, MV, Cavanagh, JB, Glynn, P (2010) Organophosphates induce distal axonal damage, but not brain oedema, by inhibiting neuropathy target esterase. Toxicol. Appl. Pharmacol. 245, 108-115. PMID 20188121
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