Localization of mRNAs Encoding Ca2+-inhibitable Adenylyl Cyclases along the Renal Tubule

Chabardès, Danielle; Firsov, D. L.; Aarab, Lotfi; Clabecq, Aude; Bellanger, Anne-Christine; Siaume-Perez, Sylvie; Elalouf, Jean‐Marc

doi:10.1074/jbc.271.32.19264

Cited by 95 publications

(104 citation statements)

References 35 publications

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“…28 AC5 expression is found in medulla and cortical and outer medullary CD of rats. 16,29,30 We found that expression of AC5 mRNA does not change with variation in fluid intake and AC5 is not up-regulated in AC6 Ϫ/Ϫ mice. Moreover, in preliminary studies, we found that lack of AC5 does not alter basal urine osmolality (WT: 1988 Ϯ 81 and AC5 Ϫ/Ϫ mice: 2089 Ϯ 53 mmol/kg, not significant; n ϭ 4/genotype; mice were kindly provided by P. L. Han 31 ).…”

Section: Discussionmentioning

confidence: 69%

Adenylate Cyclase 6 Determines cAMP Formation and Aquaporin-2 Phosphorylation and Trafficking in Inner Medulla

Rieg

Tang²,

Murray³

et al. 2010

Journal of the American Society of Nephrology

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Arginine vasopressin (AVP) enhances water reabsorption in the renal collecting duct by vasopressin V 2 receptor (V 2 R)-mediated activation of adenylyl cyclase (AC), cAMP-promoted phosphorylation of aquaporin-2 (AQP2), and increased abundance of AQP2 on the apical membrane. Multiple isoforms of adenylate cyclase exist, and the roles of individual AC isoforms in water homeostasis are not well understood. Here, we found that levels of AC6 mRNA, the most highly expressed AC isoform in the inner medulla, inversely correlate with fluid intake. Moreover, mice lacking AC6 had lower levels of inner medullary cAMP, reduced abundance of phosphorylated AQP2 (at both serine-256 and serine-269), and lower urine osmolality than wild-type mice. Water deprivation or administration of the V 2 R agonist dDAVP did not increase urine osmolality of AC6-deficient mice to the levels of wild-type mice. Furthermore, AC6-deficient mice lacked dDAVP-promoted inner medullary cAMP formation and phosphorylation of serine-269 and had attenuated increases in both phosphorylation of serine-256 and apical membrane AQP2 trafficking. In summary, AC6 expression determines inner medullary cAMP formation and AQP2 phosphorylation and trafficking, the absence of which causes nephrogenic diabetes insipidus. The anti-diuretic hormone arginine-vasopressin (AVP) is the primary regulator of water reabsorption in the renal collecting duct (CD) and is critically involved in the regulation of water balance and maintenance of plasma osmolality. 1 AVP acts on the CD through the G s protein-coupled vasopressin V 2 receptor (V 2 R) to stimulate adenylyl cyclase (AC) and thus the synthesis of cAMP. 2 cAMP activates protein kinase A (PKA), which phosphorylates the water channel aquaporin-2 (AQP2) in its COOH-terminal tail on serine residue 256 (S256), thereby resulting in apical plasma membrane accumulation of AQP2. [3][4][5][6] In addition, cAMP-independent activation of AQP2 has been reported, which may involve V 2 R action of phosphoinositide-specific phospholipase C. 7 Other non-PKA-targeted AQP2 phosphorylation sites include S261, S264, and S269. 8 Phosphorylation of AQP2 at S264 and S269 requires prior phosphorylation of S256. 9 Immunohistochemistry showed that pS269-AQP2 localizes exclusively in the apical plasma

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Section: Discussionmentioning

confidence: 69%

Adenylate Cyclase 6 Determines cAMP Formation and Aquaporin-2 Phosphorylation and Trafficking in Inner Medulla

Rieg

Tang²,

Murray³

et al. 2010

Journal of the American Society of Nephrology

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“…As found by Northern blot analysis, at least five AC isoforms are expressed in rat kidney (type IV, type V, type VI, type VII, and type IX) [for review, see (33)]. Of these isoforms, types V and VI are inhibitable by calcium, and type VI mRNA is expressed along the entire nephron, whereas type V mRNA is restricted to the glomerulus and the initial portion of the collecting duct (34). Although, there is not definite evidence for it, the best hypothesis to explain the attenuating effect of CPA on dopamine-evoked NHE3 inhibition is a CPA-dependent suppression of AC, most probably type VI AC in the case of the low dose of CPA, whereas overall depression of AC activity may explain the effects exerted by micromolar concentrations of CPA.…”

Section: Discussionmentioning

confidence: 99%

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Sole¹,

Cerull²,

Petzke³

et al. 2003

Journal of the American Society of Nephrology

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Abstract. Regulation of renal apical Na ϩ /H ϩ exchanger 3 (NHE3) activity by adenosine has been suggested to contribute to acute control of mammalian Na ϩ homeostasis. The mechanism by which adenosine controls NHE3 activity in a renal cell line was examined. The adenosine analog, N 6 -cyclopentyladenosine (CPA) exerts a bimodal effect on NHE3: CPA concentrations Ͼ10 Ϫ8 M inactivate NHE3, whereas concentrations Ͻ10 Ϫ8 M stimulate NHE3 activity. Acute CPA-induced control of NHE3 was blocked by antagonists of A 1 adenosine receptors and inhibition of phospholipase C, pretreatment with BAPTA-AM (chelator of cellular calcium), and exposure to pertussis toxin. Stimulatory and to some extent also inhibitory CPA concentrations attenuated 8-bromo-cAMP and dopaminemediated inhibition of NHE3. BAPTA eliminated the ability of a stimulatory dose of CPA to attenuate 8-bromo-cAMP-induced suppression of NHE3 activity. Upon inhibition of protein kinase C, CPA at an inhibitory dose provoked activation of NHE3, which is partially reverted by 8-bromo-cAMP and suppressed by pre-incubation with BAPTA-AM. Cytochalasin B, an actin-modifying agent, selectively prevented downregulation but did not affect upregulation of NHE3 activity by CPA. In conclusion, these observations demonstrate that (1) CPA modulates NHE3 activity by elevation of cellular Ca 2ϩ exerting a negative control on adenylate cyclase activity, (2) protein kinase C is the determining factor leading to CPAinduced downregulation of NHE3 activity, and (3) alterations of surface NHE3 abundance may contribute to A 1 adenosine receptor-dependent inhibition of NHE3 activity.

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“…Chabardes et al 21 reported that AC-VI is expressed in thick ascending limbs and collecting ducts. In contrast, the expression of renal type-V mRNA by RT-PCR was restricted to the glomerulus and to the initial portions of the collecting duct.…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, the expression of renal type-V mRNA by RT-PCR was restricted to the glomerulus and to the initial portions of the collecting duct. 21 None of these studies looked at the JG cells. Our previous study 6 found that a calcium-inhibitable isoform(s) of adenylyl cyclase did exist within the JG cells, colocalized with renin in cytoplasmic granule-like foci, but we were unable to distinguish which isoform it was.…”

Section: Discussionmentioning

confidence: 99%

Adenylyl Cyclase Isoform V Mediates Renin Release From Juxtaglomerular Cells

et al. 2007

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Abstract-We have shown previously that decreasing intracellular calcium in the juxtaglomerular cells increases both cAMP formation and renin release. We hypothesized that this is because of an interaction between intracellular calcium and the calcium-inhibitable isoform of adenylyl cyclase, type-V. We used primary cultures of juxtaglomerular cells isolated from C-57/B6 mice at 70% to 80% confluence. Western blots were performed on isolated juxtaglomerular cells using antibodies against either of the 2 calcium inhibitable isoforms of adenylyl cyclase, types-V and -VI. Only the antibody against adenylyl cyclase-V gave us a strong band at 120 kDa as expected. There are 9 isoforms of adenylyl cyclase. They all share a similar structure that includes an intracellular N terminus followed by 2 membrane-spanning domains alternating with 2 catalytic cytoplasmic loops. 7 There are 2 adenylyl cyclase isoforms, type-V (AC-V) and type-VI (AC-VI), which are both inhibited by micromolar concentrations of [Ca ϩ2 ] i . 8 Both isoforms are found in lipid rafts in either the cell or intracellular membrane regions. 9 In addition, AC-V and AC-VI share a high amino acid sequence identity, particularly in the regions that form the enzymes catalytic unit. 10 However, the N termini of the 2 isoforms are quite divergent. 7 It has been reported that, in nonexcitable cells, AC-VI colocalizes with the calcium entry channels in the cell membrane. 11 Thus, whereas the 2 enzymes share many properties, they may also have different interactions within the cell and have different compartmentalization (such as in the surface or on intracellular membranes).Previously, 6 using an antibody that does not discriminate between the 2 isoforms, we found that either 1 or both of these calcium-inhibitable adenylyl cyclases existed within the JG cell, and their presence could explain the paradoxical effect of how decreasing [Ca ϩ2 ] i could result in a cAMPmediated stimulation of renin secretion. Although we observed a provocative colocalization of our antibody with renin on what appeared to be granule-like foci within the cytoplasm, 6 we were unable to distinguish between the 2 isoforms to answer the critical question of which calciuminhibitable isoform of adenylyl cyclase is in the JG cell and

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Localization of mRNAs Encoding Ca2+-inhibitable Adenylyl Cyclases along the Renal Tubule

Cited by 95 publications

References 35 publications

Adenylate Cyclase 6 Determines cAMP Formation and Aquaporin-2 Phosphorylation and Trafficking in Inner Medulla

Adenylate Cyclase 6 Determines cAMP Formation and Aquaporin-2 Phosphorylation and Trafficking in Inner Medulla

Bimodal Acute Effects of A1 Adenosine Receptor Activation on Na+/H+ Exchanger 3 in Opossum Kidney Cells

Adenylyl Cyclase Isoform V Mediates Renin Release From Juxtaglomerular Cells

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