Trafficking mechanism of water channel aquaporin‐2

Noda, Yumi; Sasaki, Sei

doi:10.1042/bc20040120

Cited by 74 publications

(64 citation statements)

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“…The regulation of AQP2 is based in part on the redistribution of AQP2-bearing vesicles to the apical membrane and in part on the changes in its overall abundance. These processes are predominantly regulated by the antidiuretic hormone Vp (34,36) and the cAMP-responsive element in the 5Ј-flanking region of the gene for AQP2 (29). There is, however, evidence from both in vitro and in vivo studies indicating the presence of Vp-independent mechanisms regulating the translocation and expression of this water channel.…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, this type of regulated translocation of water channels has also been demonstrated in other cell types (5). For example, vasoactive intestinal polypeptide-induced translocation of AQP5 in Brunner's gland of the duodenum is associated with bicarbonate and mucin secretion, which is essential for mucosal protection (38), while Vp-and oxytocin-triggered translocation of AQP2 to and from the PM in renal collecting tubules (19,36) is critical for renal water reabsorption. As there is considerable evidence indicating the involvement of Vp-independent mechanisms in the regulation of renal water reabsorption (19,21,25,44) and some of these mechanisms are associated with cyclic-AMP (cAMP)-protein kinase A-mediated phosphorylation of water channels, we hypothesized that secretin could modulate renal water permeability by inducing Vp-independent translocation of functional AQP2 in a similar way as in cholangiocytes.…”

mentioning

confidence: 99%

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Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption

Chu¹,

Chung²,

Lam³

et al. 2007

Molecular and Cellular Biology

119

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Aquaporin 2 (AQP2) is responsible for regulating the concentration of urine in the collecting tubules of the kidney under the control of vasopressin (Vp). Studies using Vp-deficient Brattleboro rats, however, indicated the existence of substantial Vp-independent mechanisms for membrane insertion, as well as transcriptional regulation, of this water channel. The Vp-independent mechanism(s) is clinically relevant to patients with X-linked nephrogenic diabetes insipidus (NDI) by therapeutically bypassing the dysfunctional Vp receptor. On the basis of studies with secretin receptor-null (SCTR ؊/؊ ) mice, we report here for the first time that mutation of the SCTR gene could lead to mild polydipsia and polyuria. Additionally, SCTR ؊/؊ mice were shown to have reduced renal expression of AQP2 and AQP4, as well as altered glomerular and tubular morphology, suggesting possible disturbances in the filtration and/or water reabsorption process in these animals. By using SCTR ؊/؊ mice as controls and comparing them with wild-type animals, we performed both in vivo and in vitro studies that demonstrated a role for secretin in stimulating (i) AQP2 translocation from intracellular vesicles to the plasma membrane in renal medullary tubules and (ii) expression of this water channel under hyperosmotic conditions. The present study therefore provides information for at least one of the Vp-independent mechanisms that modulate the process of renal water reabsorption. Future investigations in this direction should be important in developing therapeutic means for treating NDI patients.Secretin was originally isolated from upper intestinal mucosal extract, injection of which into the jugular vein of an anesthetized dog resulted in elevation of pancreatic and hepatic bile flow (4). The primary function of secretin in releasing bicarbonate, electrolytes, and water from pancreatic ductal epithelial cells is firmly established. Additionally, it can also stimulate electrolyte and water secretion in the epididymis, as well as bicarbonate-rich ductal bile secretion from cholangiocytes (1, 9). In cholangiocytes, a secretin-induced choleretic effect is associated with microtubule-dependent exocytotic insertion of cytoplasmic vesicles containing the water channel aquaporin 1 (AQP1) onto the apical plasma membrane (PM), leading to osmotic water movement (28). Interestingly, this type of regulated translocation of water channels has also been demonstrated in other cell types (5). For example, vasoactive intestinal polypeptide-induced translocation of AQP5 in Brunner's gland of the duodenum is associated with bicarbonate and mucin secretion, which is essential for mucosal protection (38), while Vp-and oxytocin-triggered translocation of AQP2 to and from the PM in renal collecting tubules (19, 36) is critical for renal water reabsorption. As there is considerable evidence indicating the involvement of Vp-independent mechanisms in the regulation of renal water reabsorption (19,21,25,44) and some of these mechanisms are associated with cyclic-AMP (cAMP...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption

Chu¹,

Chung²,

Lam³

et al. 2007

Molecular and Cellular Biology

119

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“…Whether AQPs play a role in intracellular organellar functions is less clear. The vasopressin-regulated water channel AQP2 is expressed in both the plasma membrane and in a recycling endosomal compartment in kidney collecting cells (2,3). Although endosomes in the kidney collecting duct are highly water-permeable (4), it is likely that their high water permeability is a consequence of dense AQP2 expression rather than a need for high endosomal water permeability.…”

Section: Functionally Significant Expression Of Aquaporin (Aqp)mentioning

confidence: 99%

Evidence against Functionally Significant Aquaporin Expression in Mitochondria

Yang

Zhao

Verkman

2006

Journal of Biological Chemistry

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where they were speculated to be involved in metabolism, apoptosis, and Parkinson disease. Here, we systematically examined the functional consequence of AQP expression in mitochondria by measurement of water and glycerol permeabilities in mitochondrial membrane preparations from rat brain, liver, and kidney and from wild-type versus knock-out mice deficient in AQPs -1, -4, or -8. Osmotic water permeability, measured by stopped-flow light scattering, was similar in all mitochondrial preparations, with a permeability coefficient P f ϳ 0.009 cm/s. Glycerol permeability was also similar (ϳ5 ؋ 10 ؊6 cm/s) in the various preparations. HgCl 2 slowed osmotic equilibration comparably in mitochondria from wild-type and AQP-deficient mice, although the slowing was explained by altered mitochondrial size rather than reduced P f . Immunoblot analysis of mouse liver mitochondria failed to detect AQP8 expression, with liver homogenates from wild-type/AQP8 null mice as positive/negative controls. Our results provide evidence against functionally significant AQP expression in mitochondria, which is consistent with the high mitochondrial surface-to-volume ratio producing millisecond osmotic equilibration, even when intrinsic membrane water permeability is not high.Functionally significant expression of aquaporin (AQP) 2 -type water channels has been demonstrated in plasma membranes in various cell types in kidney, brain, eye, glandular epithelia, endothelia, epidermis, fat, and other tissues. As demonstrated by phenotype comparisons of wild-type and AQP knock-out mice, plasma membrane AQPs are important in the urinary concentration mechanism, glandular fluid secretion, regulation of intraocular and intracranial pressures, cell migration, brain swelling, epidermal hydration, adipocyte metabolism, and other functions (1). Whether AQPs play a role in intracellular organellar functions is less clear. The vasopressin-regulated water channel AQP2 is expressed in both the plasma membrane and in a recycling endosomal compartment in kidney collecting cells (2, 3). Although endosomes in the kidney collecting duct are highly water-permeable (4), it is likely that their high water permeability is a consequence of dense AQP2 expression rather than a need for high endosomal water permeability. Indeed, the high surface-to-volume ratio of endosomes and other organelles, generally Ͼ3 ϫ 10 5 cm Ϫ1 (diameter Ͻ 200 nm) predicts very rapid osmotic equilibration times of Ͻ100 ms, even when osmotic water permeability (P f ) is low (Ͻ0.005 cm/s). Other AQPs have been reported in endosomes in some cell types, including AQP6 in the renal proximal tubule and collecting duct epithelial cells (5) and various AQPs in liver cells (6), although data are lacking on their possible cellular functions. Two recent studies reported AQP expression in mitochondria and suggested possible involvement of mitochondrial AQPs in many functions, including metabolism and apoptosis, and in the pathogenesis of neurological diseases such as Parkinson disease. Calamita et al. (7)...

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“…4H, Upper). This is characteristic of an overhydrated animal when the water pore is internalized into vesicles to prevent water reabsorption (42,43).…”

Section: Aqp2 Accumulation At the Apical Surfaces Of Akap220-ko Collementioning

confidence: 99%

AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

Whiting

Ogier

Forbush

et al. 2016

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

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Filtration through the kidney eliminates toxins, manages electrolyte balance, and controls water homeostasis. Reabsorption of water from the luminal fluid of the nephron occurs through aquaporin-2 (AQP2) water pores in principal cells that line the kidney-collecting duct. This vital process is impeded by formation of an "actin barrier" that obstructs the passive transit of AQP2 to the plasma membrane. Bidirectional control of AQP2 trafficking is managed by hormones and signaling enzymes. We have discovered that vasopressin-independent facets of this homeostatic mechanism are under the control of A-Kinase Anchoring Protein 220 (AKAP220; product of the Akap11 gene). CRISPR/Cas9 gene editing and imaging approaches show that loss of AKAP220 disrupts apical actin networks in organoid cultures. Similar defects are evident in tissue sections from AKAP220-KO mice. Biochemical analysis of AKAP220-null kidney extracts detected reduced levels of active RhoA GTPase, a well-known modulator of the actin cytoskeleton. Fluorescent imaging of kidney sections from these genetically modified mice revealed that RhoA and AQP2 accumulate at the apical surface of the collecting duct. Consequently, these animals are unable to appropriately dilute urine in response to overhydration. We propose that membrane-proximal signaling complexes constrained by AKAP220 impact the actin barrier dynamics and AQP2 trafficking to ensure water homeostasis. yet only approximately 1.5 L of urine is excreted. The majority of this water is reabsorbed from the luminal fluid of the nephron (1). Regulated water reabsorption in response to dehydration occurs through aquaporin-2 (AQP2) water pores in the principal cells of the collecting duct (2). This is stimulated by the hormone arginine vasopressin (AVP). Vasopressin induces PKA phosphorylation of serine 256 on AQP2 and stimulates its translocation from intracellular vesicles to the apical membranes of cells lining the collecting ducts. Reabsorption of water through the kidney preserves fluid balance and results in more concentrated urine (3, 4). Conversely, when an animal ingests excess water, decreased plasma osmolality inhibits vasopressin release, and AQP2 is recovered from the apical membrane by endocytosis. This renders the collecting duct impermeable to water, thereby diverting excess water through the ureter to the bladder.Not surprisingly, defects in AQP2 trafficking have pathophysiological outcomes. For example, nephrogenic diabetes insipidus (NDI) is associated with impaired vasopressin signaling to AQP2 (5-8). Symptoms include excessive thirst, excretion of a large volume of dilute urine, and electrolyte imbalances, including hypernatremia (1, 5). Hereditary forms of this disease appear in patients with inactivating mutations in the V2 vasopressin receptor (V2R) or AQP2 (9-12). Thus, understanding the molecular mechanisms that govern bidirectional control of AQP2 location may lead to new therapeutic approaches for the treatment of NDI.Although the enzymes and effector proteins that govern AQP2 in...

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Trafficking mechanism of water channel aquaporin‐2

Cited by 74 publications

References 86 publications

Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption

Phenotypes Developed in Secretin Receptor-Null Mice Indicated a Role for Secretin in Regulating Renal Water Reabsorption

Evidence against Functionally Significant Aquaporin Expression in Mitochondria

AKAP220 manages apical actin networks that coordinate aquaporin-2 location and renal water reabsorption

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