Molecular Basis of pH and Ca2+ Regulation of Aquaporin Water Permeability

Németh-Cahalan, Karin L.; Kálmán, Katalin; Hall, James E.

doi:10.1085/jgp.200308990

Cited by 143 publications

(182 citation statements)

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“…AQP0 water conductance is pH-dependent with a maximum at pH 6.5 and only about half the activity at pH 10.5 12 . These conductance characteristics are not changed by proteolytic cleavage of AQP0 24 .…”

Section: Water Molecules In the Aqp0 Porementioning

confidence: 99%

“…The structure showed that AQP0 junctions are stabilised by specific interactions between tetramers in adjoining membranes involving almost exclusively proline residues. Calculated pore profiles also showed that the pore in junctional AQP0 is highly constricted due to a substantially extended ar/R constriction site and a novel second constriction site 7 , which may be involved in the pH regulation of AQP0 water conductance 12 .…”

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confidence: 90%

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Lipid–protein interactions in double-layered two-dimensional AQP0 crystals

Gonen

Cheng

Sliz

et al. 2005

Nature

617

644

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Lens-specific aquaporin-0 (AQP0) functions as a specific water pore and forms the thin junctions between fibre cells. We describe a 1.9 Å resolution structure of junctional AQP0, determined by electron crystallography of double-layered two-dimensional crystals. Comparison of junctional and non-junctional AQP0 structures shows that junction formation depends on a conformational switch in an extracellular loop, which may result from cleavage of the cytoplasmic N-and C-termini. In the centre of the water pathway, the closed pore in junctional AQP0 retains only three water molecules, which are too widely spaced to form hydrogen bonds with each other. Packing interactions between AQP0 tetramers in the crystalline array are mediated by lipid molecules, which assume preferred conformations. We could therefore build an atomic model for the lipid bilayer surrounding the AQP0 tetramers, and we describe lipid-protein interactions. KeywordsAquaporin-0; lens; MIP; two-dimensional crystal; lipid-protein interaction; electron crystallography Members of the aquaporin (AQP) family form membrane pores that are either highly selective for water (aquaporins) or also permeable to other small neutral solutes such as glycerol and urea (aquaglyceroporins) (reviewed in 1 ). Structural studies have revealed that all AQPs share the same basic architecture, which consists of two tandem repeats, each containing a bundle of three transmembrane α-helices and a hydrophobic loop with the highly conserved asparagine-proline-alanine (NPA) motif 2 -8 . The two NPA-containing loops B and E fold back into the membrane and form short α-helices (HB and HE) that line the water pore. The ar/R constriction site, so named because it is formed by an aromatic and an arginine residue, confers water selectivity to AQP pores, while the NPA motifs play an important role in the proton exclusion mechanism (reviewed in 9 ).Correspondence to: Thomas Walz.Correspondence and requests for materials should be addressed to T.W. (twalz@hms.harvard.edu). Coordinates and structure factors for junctional and non-junctional AQP0 have been deposited in the Protein Data Bank (accession codes 2B6O and 2B6P, respectively).. Suplementary Information accompanies the paper on www.nature.com/nature. Competing interests statementThe authors declare that they have no competing financial interests. AQP0 is the most abundant protein in lens fibre cell membranes, where it forms not only water pores but also the 11-13 nm "thin lens junctions" that assemble upon proteolytic cleavage of the cytoplasmic termini 10 , 11 . We recently presented the structure of the AQP0-mediated membrane junction at 3 Å resolution as determined by electron crystallography of doublelayered two-dimensional (2D) crystals 7 . The structure showed that AQP0 junctions are stabilised by specific interactions between tetramers in adjoining membranes involving almost exclusively proline residues. Calculated pore profiles also showed that the pore in junctional AQP0 is highly constricted due to a substantially ...

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Section: Water Molecules In the Aqp0 Porementioning

confidence: 99%

mentioning

confidence: 90%

Lipid–protein interactions in double-layered two-dimensional AQP0 crystals

Gonen

Cheng

Sliz

et al. 2005

Nature

617

644

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“…they are not constitutively locked into a rigid open state. For instance, the lens water channel AQP0 as well as plant aquaporins show changes in water permeability as a function of pH (37,38 (39,40) and the closely related AQP4 (41). Aquaporins are highly conserved in animals and plants.…”

Section: Pharmacological Agonists Of the Aquaporinsmentioning

confidence: 99%

Water transport across the peritoneal membrane

Devuyst

Rippe

2014

Kidney International

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Peritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a three-pore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haploinsufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small-solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open-state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated. ABSTRACTPeritoneal dialysis involves diffusive and convective transports and osmosis through the highly vascularized peritoneal membrane. The capillary endothelium offers the rate-limiting hindrance for solute and water transport. It can be functionally described in terms of a threepore model including transcellular, ultrasmall pores responsible for free-water transport during crystalloid osmosis. Several lines of evidence have demonstrated that the water channel aquaporin-1 (AQP1) corresponds to the ultrasmall pore located in endothelial cells. Studies in Aqp1 mice have shown that deletion of AQP1 is reflected by a 50% decrease in ultrafiltration and a disappearance of the sodium sieving. Haplo-insufficiency in AQP1 is also reflected by a significant attenuation of water transport. Conversely, studies in a rat model and in PD patients have shown that the induction of AQP1 in peritoneal capillaries by corticosteroids is reflected by increased water transport and ultrafiltration, without affecting the osmotic gradient and small solute transport. Recent data have demonstrated that a novel agonist of AQP1, predicted to stabilize the open state conformation of the channel, modulates water transport and improves ultrafiltration. Whether increasing the expression of AQP1 or gating the already existing channels would be clinically useful in PD patients remains to be investigated.The development of peritoneal dialysis (PD) as a successful therapy for patients with end stage renal disease has been paralleled by the need to understand the transport mechanisms operating in the peritoneal membrane. Functional alterations in the dialysis capacity of the...

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“…Alterations in pH and calcium concentration, through interaction with specific histidine residues within the AQP pore have also been shown to cause different effects on water permeability in bovine and fish AQPs, despite sharing approximately 70% of their sequence (Nemeth-Cahalan et al, 2004). Regulation via gating mechanisms, which allow conformationally distinct open and closed states, has specifically been reported for plant and microbial AQPs (Tornroth-Horsefield et al, 2006).…”

Section: What Regulates Aqp Function?mentioning

confidence: 99%

An emerging consensus on aquaporin translocation as a regulatory mechanism

Conner

Bill

Conner

2012

Molecular Membrane Biology

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Water can pass through the cell membrane relatively slowly by diffusion. However, in order to maintain water homeostasis, the rapid and specific regulation of cellular water flow is mediated by the aquaporin (AQP) family of membrane protein water channels. Thirteen human AQPs have been identified to date and the majority are highly specific for water while others show selectivity for water, glycerol and other small solutes. The wide range of tissues that are known to express AQPs is reflected by their involvement in many physiological processes and diseases. Receptor mediated translocation, via hormone activation, is an established method of AQP regulation, especially for AQP2. There is now an emerging consensus that the rapid and reversible translocation of other AQPs from intracellular vesicles to the plasma membrane, triggered by a range of stimuli, can confer increased membrane permeability. This review examines new advances that have identified molecular mechanisms of AQP regulation; these include the role of cytoskeletal proteins, kinases, calcium and retention or localisation signals as well as specific triggers of AQP translocation. This article reviews current knowledge of AQP regulation with a focus on rapid and dynamic regulation of sub-cellular AQP translocation in response to a specific trigger.3

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Molecular Basis of pH and Ca2+ Regulation of Aquaporin Water Permeability

Cited by 143 publications

References 41 publications

Lipid–protein interactions in double-layered two-dimensional AQP0 crystals

Lipid–protein interactions in double-layered two-dimensional AQP0 crystals

Water transport across the peritoneal membrane

An emerging consensus on aquaporin translocation as a regulatory mechanism

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