Aquaporin gating

Hedfalk, Kristina; Törnroth-Horsefield, Susanna; Nyblom, Maria; Johanson, Urban; Kjellbom, Per; Neutze, Richard

doi:10.1016/j.sbi.2006.06.009

Cited by 120 publications

(104 citation statements)

References 80 publications

Supporting

Mentioning

101

Contrasting

Order By: Relevance

“…There is increasing evidence that aquaporins are gated (28). The spinach aquaporin SoPIP2;1 is gated by phosphorylation at Ser-115 and Ser-274 (29).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Aquaporin-2 Regulates Its Water Permeability

Eto

Noda

Horikawa

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

Vasopressin-regulated water reabsorption through the water channel aquaporin-2 (AQP2) in renal collecting ducts maintains body water homeostasis. Vasopressin activates PKA, which phosphorylates AQP2, and this phosphorylation event is required to increase the water permeability and water reabsorption of the collecting duct cells. It has been established that the phosphorylation of AQP2 induces its apical membrane insertion, rendering the cell water-permeable. However, whether this phosphorylation regulates the water permeability of this channel still remains unclear. To clarify the role of AQP2 phosphorylation in water permeability, we expressed recombinant human AQP2 in Escherichia coli, purified it, and reconstituted it into proteoliposomes. AQP2 proteins not reconstituted into liposomes were removed by fractionating on density step gradients. AQP2-reconstituted liposomes were then extruded through polycarbonate filters to obtain unilamellar vesicles. PKA phosphorylation significantly increased the osmotic water permeability of AQP2-reconstituted liposomes. We then examined the roles of AQP2 phosphorylation at Ser-256 and Ser-261 in the regulation of water permeability using phosphorylation mutants reconstituted into proteoliposomes. The water permeability of the non-phosphorylationmimicking mutant S256A-AQP2 and non-phosphorylated WT-AQP2 was similar, and that of the phosphorylation-mimicking mutant S256D-AQP2 and phosphorylated WT-AQP2 was similar. The water permeability of S261A-AQP2 and S261D-AQP2 was similar to that of non-phosphorylated WT-AQP2. This study shows that PKA phosphorylation of AQP2 at Ser-256 enhances its water permeability.Body water homeostasis is essential for the survival of mammals and is regulated by the renal collecting duct. Key components in the regulation of collecting duct water permeability are the vasopressin receptor and the water channel aquaporin-2 (AQP2) 2 (1-6). Mutations in the vasopressin V 2 receptor and AQP2 cause congenital nephrogenic diabetes insipidus, a disease characterized by a massive loss of water through the kidney (7,8). The binding of the antidiuretic hormone vasopressin to vasopressin V 2 receptors on renal principal cells stimulates cAMP synthesis via activation of adenylate cyclase. The subsequent activation of PKA leads to phosphorylation of AQP2 at Ser-256, and this phosphorylation event is required to increase the water permeability and water reabsorption of renal principal cells. It has been established that the phosphorylation of AQP2 induces its apical membrane insertion, rendering the cell water-permeable. We showed recently that AQP2 binds to a multiprotein "motor" complex and that phosphorylation-dependent reciprocal interaction with G-actin and tropomyosin 5b directs AQP2 to the apical membrane (9 -13). However, whether this phosphorylation regulates the water permeability of individual AQP2 proteins still remains unclear. Kuwahara et al. (14) showed that cAMP stimulation increased the water permeability of AQP2 expressed in Xenopus oocytes, alt...

show abstract

“…There is increasing evidence that aquaporins are gated (28). The spinach aquaporin SoPIP2;1 is gated by phosphorylation at Ser-115 and Ser-274 (29).…”

Section: Discussionmentioning

confidence: 99%

Phosphorylation of Aquaporin-2 Regulates Its Water Permeability

Eto

Noda

Horikawa

et al. 2010

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…AQP4 conductance is reduced Ͼ50% by phosphorylation mediated by protein kinase C at Ser-180 (18,19), and increased Ϸ40% by protein kinase G activity at Ser-111 (20). The gating mechanism by phosphorylation events may be similar to that of the spinach AQP SoPIP2;1 (21,22).…”

Section: T He Aquaporin (Aqp) Family Includes Both Aqps That Conductmentioning

confidence: 94%

Crystal structure of human aquaporin 4 at 1.8 Å and its mechanism of conductance

Yeh

Sandstrom

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

305

298

View full text Add to dashboard Cite

Aquaporin (AQP) 4 is the predominant water channel in the mammalian brain, abundantly expressed in the blood-brain and braincerebrospinal fluid interfaces of glial cells. Its function in cerebral water balance has implications in neuropathological disorders, including brain edema, stroke, and head injuries. The 1.8-Å crystal structure reveals the molecular basis for the water selectivity of the channel. Unlike the case in the structures of water-selective AQPs AqpZ and AQP1, the asparagines of the 2 Asn-Pro-Ala motifs do not hydrogen bond to the same water molecule; instead, they bond to 2 different water molecules in the center of the channel. Molecular dynamics simulations were performed to ask how this observation bears on the proposed mechanisms for how AQPs remain totally insulating to any proton conductance while maintaining a single file of hydrogen bonded water molecules throughout the channel.brain edema ͉ inhibitor discovery ͉ NPA motif

show abstract

“…Such adaptations are especially evident in the lens of the mammalian eye, where many of the usual cellular metabolic pathways have been sacrificed to achieve one overriding goal: transparency. The lens is nonetheless metabolically active, and water balance is critical to lens homeostasis over the lifetime of an animal, as demonstrated by the abundance of the water transporter AQP0, which accounts for Ͼ60% of the membrane protein component in lens fiber cells (1)(2)(3)(4)(5). Originally designated the major intrinsic protein of the lens, AQP0 is the founding member of the aquaporin family (6); aquaporins have been studied extensively as a result of their central role in ensuring water balance across all kingdoms of life (2,3,7,8).…”

mentioning

confidence: 99%

Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens

Jensen

Dror

et al. 2008

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Aquaporin 0 (AQP0), the most abundant membrane protein in mammalian lens fiber cells, not only serves as the primary water channel in this tissue but also appears to mediate the formation of thin junctions between fiber cells. AQP0 is remarkably less water permeable than other aquaporins, but the structural basis and biological significance of this low permeability remain uncertain, as does the permeability of the protein in a reported junctional form. To address these issues, we performed molecular dynamics (MD) simulations of water transport through membrane-embedded AQP0 in both its (octameric) junctional and (tetrameric) nonjunctional forms. From our simulations, we measured an osmotic permeability for the nonjunctional form that agrees with experiment and found that the distinct dynamics of the conserved, lumen-protruding side chains of Tyr-23 and Tyr-149 modulate water passage, accounting for the slow permeation. The junctional and nonjunctional forms conducted water equivalently, in contrast to a previous suggestion based on static crystal structures that water conduction is lost on junction formation. Our analysis suggests that the low water permeability of AQP0 may help maintain the mechanical stability of the junction. We hypothesize that the structural features leading to low permeability may have evolved in part to allow AQP0 to form junctions that both conduct water and contribute to the organizational structure of the fiber cell tissue and microcirculation within it, as required to maintain transparency of the lens.membrane ͉ MD simulation ͉ water channel ͉ permeability ͉ cell adhesion

show abstract

Aquaporin gating

Cited by 120 publications

References 80 publications

Phosphorylation of Aquaporin-2 Regulates Its Water Permeability

Phosphorylation of Aquaporin-2 Regulates Its Water Permeability

Crystal structure of human aquaporin 4 at 1.8 Å and its mechanism of conductance

Dynamic control of slow water transport by aquaporin 0: Implications for hydration and junction stability in the eye lens

Contact Info

Product

Resources

About