Aquaporins

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Aquaporins
Aquaporins
Band representation of the AQP1
Properties of human protein
Identifier
Gene names MIP , AQP1, AQP2, AQP3
Transporter classification
TCDB 1.A.8
designation MIP / aquaporin family
Occurrence
Parent taxon Creature

Representation of an aquaporin channel (cut open). The pore in the middle of the homotetramer does not conduct water.

Aquaporins ( AQP ) are proteins that form channels in the cell membrane to facilitate the passage of water and some other molecules ( membrane transport ). They are therefore also called water channels . Aquaporins occur in all living things with a cell membrane; they have been found in archaea , bacteria, and eukaryotes .

Since biomembranes are water-repellent ( hydrophobic ) inside , their conductivity for water molecules is very low. The water conductivity of an aquaporin channel, on the other hand, is up to 3 billion molecules per second. The protein family of aquaporins is divided into so-called common aquaporins and aquaglyceroporins. Ordinary aquaporins are pure water channels. Aquaglyceroporine also conduct small organic molecules such as glycerine or urea . Under physiological conditions, aquaporins act as tetramers ; H. four aquaporin channels are built into a biological membrane as a unit.

History

The fact that water can be transported through cell membranes has long been known. The first speculations and discussions about the mechanism go back to the middle of the 19th century (among others Ernst Wilhelm Brücke was involved). After the discovery of the double lipid layer in plasma membranes in the late 1920s , the simple diffusion of water through the cell membrane was assumed, but could not explain the vastly different permeabilities of different cells. In the 1970s u. a. by Arthur Solomon, Robert Macey and Alan Finkelstein postulated the existence of specific water channels on the basis of biophysical models. The problem of identification is quite complex: water is everywhere and it cannot be modified by photosensitive side chains. Attempts at genetic cloning of the corresponding proteins were also unsuccessful.

It was not until the early 1990s that Peter Agre's working group succeeded in identifying a protein (CHIP28) known from earlier studies on rhesus blood group antigens with a previously unknown function as the water channel we were looking for. They then named this protein aquaporin-1 (AQP1). In 2003 he received the Nobel Prize in Chemistry for his research in the field of aquaporins . To date, a number of aquaporins have been identified in humans, animals, plants and bacteria.

structure

Membrane orientation of the AQP1 protein.

All known aquaporins have a similar structure and amino acid sequence . The primary structure of AQP1 consists of 268 amino acids . These form six α-helices that span the membrane ( integral membrane protein ). The helices are connected to one another via loops A to E. Loops B and E play a special role, each forming a short helix that plunges into the membrane from both sides up to the middle. On each of the two loops, at the end of the two short helices , there is a characteristic structural motif, consisting of three amino acids (N – P – A, asparagine - proline - alanine ), which contributes significantly to the selectivity of the water channel. Each of the two loops forms a half-pore, which together form a water channel ( hour-glass model , hourglass model ). The channel is narrowest in the middle (0.3 nm), and the diameter of the two openings is 2 nm. The carboxy and amino terminal ends of the membrane protein are inside the cell. In biological membranes, aquaporins form homotetramers, which means that four single-functional pore proteins attach to one another.

function

Water can only diffuse to a limited extent through the double lipid layer of the cell membrane. Cells with very high water permeability, such as renal tubular cells , secreting cells of the salivary glands or erythrocytes, need the help of water channels for rapid water exchange. The difference between diffusion and channel-mediated permeability is significant. Diffusion is a process that occurs with little capacity in both directions through the membrane of all cells. In the presence of specific water channels, the water can move almost unhindered in the direction of the osmotic gradient. The aquaporins are not pumps or exchangers and no metabolic energy is used for transport. The channel works bidirectionally, i. H. Water can travel through the canal in either direction. While the diffusion through the membranes cannot be blocked, the aquaporins can be blocked by molecules that clog their pores, thereby interrupting the flow of water. Some aquaporins can become clogged with mercury compounds that covalently bind to a cysteine ​​side chain in the pore.

Proton blockade

Aquaporins are highly selective. In particular, they prevent the conduction of protons across the membrane so that the proton gradient , which is vital for every cell , is not destroyed. (The proton gradient is used to enable transport processes - see e.g. ATPases ). This is not a matter of course, since water in the liquid phase is not present as a single molecule, but rather as a network connected by hydrogen bonds . Protons can hop from molecule to molecule along these hydrogen bonds ( Grotthuss mechanism ).

How the hopping of protons through the channel is prevented is the subject of current research. What seems to be important is that aquaporins, due to their structure, form an electrostatic barrier in the middle of the channel. This has the consequence that the polar water molecules with their partially negatively charged oxygen are mostly oriented towards the center of the channel, while the partially positively charged hydrogens are mostly oriented toward the channel exits. Early work (2002) therefore assumed that the orientation of the water molecules interrupted the Grotthuss mechanism.

More recent works question this interpretation and focus on the energetic barrier that the proton has to overcome along the channel. The subject of the current debate (as of July 2007) is the origin of the energetic barrier. While some scientists emphasize the electrostatic barrier created by the protein, others point out that the protein cannot replace the solvation envelope of a proton / oxonium ion in water.

Inhibition

Aquaporin-1 is inhibited (inhibited) by mercury , gold or silver ions . The ion binds to a cysteine in the pore entrance and thus blocks the flow of water. These ions do not specifically bind to aquaporin-1 and are therefore toxic. The discovery of a non-toxic inhibitor was published in 2009, it is a derivative of the loop diuretic bumetanide and was designated in the publication as AqB013. This substance showed an antagonistic effect against aquaporin-1 and -4. The search for further specific aquaporin inhibitors is the subject of current research.

Facilitated cellular water diffusion in plants

The function of aquaporins in plant cells could be characterized as components of the facilitated cellular water diffusion and their occurrence could be proven in plant tissue. A certain aquaporin protein class facilitates the diffusion of CO 2 in plant tissue and cells or chloroplasts.

meaning

The aquaporins are of physiological importance especially in tissues in which a high physiological flow occurs, e.g. B. when building up the turgor pressure in plant cells.

Malfunction of the aquaporins is responsible for diseases such as diabetes insipidus renalis , cataracts , glaucoma (green star) and hearing loss . Antibodies against aquaporin 4 cause neuromyelitis optica spectrum diseases in the central nervous system . Aquaporins also play a role in the occurrence of brain edema after a traumatic brain injury .

nomenclature

  • Aquaporins of animal origin are simply numbered (AQP1, AQP4). Usually the corresponding Latin generic name is added in front, for example bovAQP1 (Latin bos , bovis = cattle).
  • Aquaporins of vegetable origin are named differently. 1 that there is a, so AtTIP2 means tonoplast intrinsic protein of the (model) plant thale cress ( Arabidopsis thaliana is).

variants

CHIPs ( channel-forming integral proteins ) are located in the cell membrane of red blood cells and kidney cells. In mammals, the density of aquaporins is particularly high in erythrocytes (approx. 200,000 channels per cell) and in the proximal tubular cells of the kidney, which absorb the water when urine is formed.

AQP2, which occurs in cells of the collecting ducts of the kidney (hence the old name WCHDs from English water channels of collecting duct ) is stored in vesicles . When there is a lack of water, the pituitary gland releases the hormone vasopressin . Vasopressin binds to certain membrane receptors of AQP2-containing cells and sets off a signal cascade . This causes the vesicles to fuse with the cell membrane, increasing the absorption of water from the primary urine by a factor of twenty.

TIPs ( tonoplast intrinsic proteins ) are integrated into the membrane of the vacuole in plants and ensure that the cell increases in volume through water absorption during cell growth.

PIPs ( plasma membrane intrinsic proteins ) are also only found in plants and regulate the water conduction through the cells. In this way there is a second water transport system through the other plant tissues in addition to the water supply vessels of the xylem .

Nobel Prize

Roderick MacKinnon (Rockefeller University, New York) and Peter Agre (Johns Hopkins University, Baltimore) received the 2003 Nobel Prize in Chemistry for their research on aquaporins and potassium channels .

Individual evidence

  1. ↑ Frings, Stephan, Möhrlen, Frank: Animal and Human Physiology An introduction . 5th, revised. u. updated edition 2015. Springer Berlin Heidelberg, Berlin, Heidelberg 2015, ISBN 978-3-662-43942-5 .
  2. ↑ Information from the Nobel Foundation on the 2003 award ceremony to Peter Agre (English)
  3. ↑ Kaldenhoff , R., A. Kolling, and G. Richter, A Novel Blue Light-Inducible and Abscisic Acid-Inducible Gene of Arabidopsis-Thaliana Encoding An Intrinsic Membrane-Protein. Plant Molecular Biology, 1993. 23 (6): p. 1187-1198.
  4. ↑ UniProt P29972
  5. ↑ Macey RI, Farmer RE. Inhibition of water and solute permeability in human red cells (1970) Biochim Biophys Acta. 1970 Jul 7; 211 (1): p. 104-106.
  6. ↑ Elton Migliati, Nathalie Meurice, Pascale DuBois, Jennifer S. Fang, Suma Somasekharan: Inhibition of Aquaporin-1 and Aquaporin-4 Water Permeability by a Derivative of the Loop Diuretic Bumetanide Acting at an Internal Pore-Occluding Binding Site . May 23, 2017, p. 105–112 , doi : 10.1124 / mol.108.053744 , PMID 19403703 , PMC 2701455 (free full text).
  7. ↑ Kaldenhoff, R., A. Kolling, J. Meyers, U. Karmann, G. Ruppel, and G. Richter, The blue light-responsive AthH2 gene of Arabidopsis thaliana is primarily expressed in expanding as well as in differentiating cells and encodes a putative channel protein of the plasmalemma. The Plant journal: for cell and molecular biology, 1995. 7 (1): p. 87-95
  8. ↑ Biela, A., K. Grote, B. Otto, S. Hoth, R. Hedrich, and R. Kaldenhoff, The Nicotiana tabacum plasma membrane aquaporin NtAQP1 is mercury-insensitive and permeable for glycerol. The Plant journal: for cell and molecular biology, 1999. 18 (5): p. 565-70.
  9. ↑ Siefritz, F., MT Tyree, C. Lovisolo, A. Schubert, and R. Kaldenhoff, PIP1 plasma membrane aquaporins in tobacco: from cellular effects to function in plants. Plant Cell, 2002. 14 (4): p. 869-76.
  10. ↑ Otto, B. and R. Kaldenhoff, Cell-specific expression of the mercury-insensitive plasma-membrane aquaporin NtAQP1 from Nicotiana tabacum. Planta, 2000. 211 (2): p. 167-72.
  11. ↑ Otto, B., N. Uehlein, S. Sdorra, M. Fischer, M. Ayaz, X.astenegui-Macadam, M. Heckwolf, M. Lachnit, N. Pede, N. Priem, A. Reinhard, S. Siegfart, M. Urban, and R. Kaldenhoff, Aquaporin tetramer composition modifies the function of tobacco aquaporins. Journal of Biological Chemistry, 2010. 285 (41): p. 31253-60
  12. ↑ Uehlein, N., C. Lovisolo, F. Siefritz, and R. Kaldenhoff, The tobacco aquaporin NtAQP1 is a membrane CO 2 pore with physiological functions. Nature, 2003. 425 (6959): p. 734-7.
  13. ↑ Uehlein, N., B. Otto, D. Hanson, M. Fischer, N. McDowell, and R. Kaldenhoff, Function of Nicotiana tabacum aquaporins as chloroplast gas pores challenges the concept of membrane CO 2 permeability. Plant Cell, 2008. 20 (3): p. 648-57.
  14. ↑ Flexas, J., M. Ribas-Carbo, DT Hanson, J. Bota, B. Otto, J. Cifre, N. McDowell, H. Medrano, and R. Kaldenhoff, Tobacco aquaporin NtAQP1 is involved in mesophyll conductance to CO 2 in vivo. Plant Journal, 2006. 48 (3): p. 427-39.
  15. ↑ Heckwolf, M., D. Pater, DT Hanson, and R. Kaldenhoff, The Arabidopsis thaliana aquaporin AtPIP1; 2 is a physiologically relevant CO transport facilitator. The Plant journal: for cell and molecular biology, 2011. 67 (5): p. 795-804.
  16. ↑ Verkman AS. (2002): Aquaporin water channels and endothelial cell function. In: J. Anat. 200 (6): 617-627. PMID 12162729 , PMC 1570747 (free full text)

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