Cyclic AMP is sufficient for triggering the exocytic recruitment of aquaporin‐2 in renal epithelial cells

Lorenz, Dorothea; Krylov, Andrey V.; Hahm, Daniel; Hagen, Volker; Rosenthal, Walter; Pohl, Peter; Maric, Kenan

doi:10.1038/sj.embor.embor711

Cited by 72 publications

(51 citation statements)

References 23 publications

(31 reference statements)

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“…6,7,34,35 In extreme situations of water deprivation (e.g., hypovolaemia) short-and longterm regulation may not sufficiently prevent dehydration. An AVP-dependent reduction of AQP2 pUb, increasing the AQP2 abundance in the short term (Figure 3), substantiates shortand long-term regulations by further enhancing water re-absorption.…”

Section: Discussionmentioning

confidence: 99%

Reciprocal Regulation of Aquaporin-2 Abundance and Degradation by Protein Kinase A and p38-MAP Kinase

Nedvetsky

Tabor

Tamma

et al. 2010

Journal of the American Society of Nephrology

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106

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Arginine-vasopressin (AVP) modulates the water channel aquaporin-2 (AQP2) in the renal collecting duct to maintain homeostasis of body water. AVP binds to vasopressin V2 receptors (V2R), increasing cAMP, which promotes the redistribution of AQP2 from intracellular vesicles into the plasma membrane. cAMP also increases AQP2 transcription, but whether altered degradation also modulates AQP2 protein levels is not well understood. Here, elevation of cAMP increased AQP2 protein levels within 30 minutes in primary inner medullary collecting duct (IMCD) cells, in human embryonic kidney (HEK) 293 cells ectopically expressing AQP2, and in mouse kidneys. Accelerated transcription or translation did not explain this increase in AQP2 abundance. In IMCD cells, cAMP inhibited p38-mitogen-activated protein kinase (p38-MAPK) via activation of protein kinase A (PKA). Inhibition of p38-MAPK associated with decreased phosphorylation (serine 261) and polyubiquitination of AQP2, preventing proteasomal degradation. Our results demonstrate that AVP enhances AQP2 protein abundance by altering its proteasomal degradation through a PKA-and p38-MAPK-dependent pathway. Aquaporin-2 (AQP2) is the water channel mediating arginine-vasopressin (AVP)-increases in water re-absorption in renal collecting duct principal cells. 1-4 AVP binds to plasma membrane-located vasopressin V2 receptors, thereby stimulating adenylyl cyclase and elevating cAMP. cAMP activates protein kinase A (PKA), which phosphorylates AQP2 at serine 256 (S256), inducing its redistribution from intracellular vesicles into the plasma membrane. 3,4 This short-term regulation of AQP2 occurs within seconds to minutes. In the case of long-term regulation, cAMP enhances AQP2 mRNA expression, followed by a rise in the AQP2 protein level within hours. 5,6 AQP2 can be degraded in proteasomes and lysosomes. 7,8 Ubiquitination directs proteins for degradation to both compartments. Monoubiquitination (mUb) is a signal for degradation in lysosomes, whereas polyubiquitination (pUb) is mainly linked to proteasomal degradation. 9 mUb of AQP2 is induced by FSK stimulation and occurs at the apical plasma membrane. 10 In WT5 cells, a model for AQP2 regulation, increased mUb of AQP2 persists

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Section: Discussionmentioning

confidence: 99%

Reciprocal Regulation of Aquaporin-2 Abundance and Degradation by Protein Kinase A and p38-MAP Kinase

Nedvetsky

Tabor

Tamma

et al. 2010

Journal of the American Society of Nephrology

Self Cite

106

129

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“…8) (26,32,35,47,53,54). Whereas in control cells, AQP2 was found mainly intracellularly, it was predominantly located at the plasma membrane in AVP-treated cells (Fig.…”

Section: Aqp2 and Akap18␦ Co-localize In Imcd Cells And Co-translocatmentioning

confidence: 99%

“…Except for renin secretion from juxtaglomerular kidney cells, the AVP-induced AQP2 translocation is the only example of an exocytic process solely triggered by cAMP (54). Some other exocytic processes such as proton secretion from gastric parietal cells may be triggered by cAMP or Ca 2ϩ increases, and yet others are strictly dependent on Ca 2ϩ increases and are only modulated by cAMP (for review see Ref.…”

Section: Fig 3 Akap18␦ Functions As An Akap In Vivomentioning

confidence: 99%

Identification of a Novel A-kinase Anchoring Protein 18 Isoform and Evidence for Its Role in the Vasopressin-induced Aquaporin-2 Shuttle in Renal Principal Cells

Henn

Edemir

Stefan

et al. 2004

Journal of Biological Chemistry

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“…AVP causes its redistribution, predominantly into the basolateral plasma membrane (2,17,19,22,23) (➜, 18 nm of gold particles) and PDE4D (3, 10 nm of gold particles) were detected by using the same primary antibodies as in C (Bar ϭ 500 nm). The lower image was assembled from two separately recorded images using analySIS software.…”

Section: Inhibition Of Pde4 Increases Pf and The Aqp2 Shuttlementioning

confidence: 99%

Compartmentalization of cAMP-Dependent Signaling by Phosphodiesterase-4D Is Involved in the Regulation of Vasopressin-Mediated Water Reabsorption in Renal Principal Cells

Stefan

Wiesner

Baillie

et al. 2007

Journal of the American Society of Nephrology

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A ntidiuretic hormone (arginine vasopressin [AVP]) induces fusion of vesicles that contain the water channel aquaporin-2 (AQP2) with the plasma membrane of renal collecting duct principal cells. This "AQP2 shuttle" increases the osmotic water permeability (Pf) of the cells, facilitating water reabsorption from the collecting duct (1). The AQP2 shuttle is initiated upon binding of AVP to vasopressin-2 receptors (V2R) and triggered by the consequent cAMP elevation and protein kinase A (PKA) activation. It is the PKA phosphorylation of AQP2 that elicits redistribution of AQP2-bearing vesicles. Pivotal to this redistribution is the compartmentalization of PKA by A kinase anchoring proteins (AKAP) (2). Phosphodiesterases (PDE), which are the sole means of degrading cAMP, are poised to regulate PKA signaling (3-6). The PDE4 family has attracted great interest because of its link to stroke (7), schizophrenia (8), and the therapeutic potential of selective inhibitors for treating inflammatory diseases (9-12). The four subfamilies (PDE4A through D) are encoded by separate genes, generating approximately 20 isoforms (9,11) that can interact with scaffolding proteins, including AKAP and ␤-arrestin (12-16), positioning them for a role in compartmentalized cAMP/PKA signaling.Here we show that compartmentalization of cAMP/PKA signaling by PDE4 is involved in the regulation of the AQP2 shuttle and the Pf. This is of particular pertinence because PDE4 hyperactivity causes nephrogenic diabetes insipidus in a mouse model (17).

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Cyclic AMP is sufficient for triggering the exocytic recruitment of aquaporin‐2 in renal epithelial cells

Cited by 72 publications

References 23 publications

Reciprocal Regulation of Aquaporin-2 Abundance and Degradation by Protein Kinase A and p38-MAP Kinase

Reciprocal Regulation of Aquaporin-2 Abundance and Degradation by Protein Kinase A and p38-MAP Kinase

Identification of a Novel A-kinase Anchoring Protein 18 Isoform and Evidence for Its Role in the Vasopressin-induced Aquaporin-2 Shuttle in Renal Principal Cells

Compartmentalization of cAMP-Dependent Signaling by Phosphodiesterase-4D Is Involved in the Regulation of Vasopressin-Mediated Water Reabsorption in Renal Principal Cells

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