Skip to main content

Advertisement

SpringerLink
Log in

Calcium signaling in vasopressin-induced aquaporin-2 trafficking

  • Invited Review
  • Published:
Pflügers Archiv - European Journal of Physiology Aims and scope Submit manuscript

Abstract

It has been the general consensus that cAMP-mediated PKA-dependent phosphorylation of aquaporin-2 is the primary mechanism of vasopressin to regulate osmotic water permeability in kidney collecting duct. By using laser scanning confocal microscopy to monitor [Ca2+]i and apical exocytosis in individual cells of inner medullary collecting duct, we have demonstrated that vasopressin also triggers intracellular Ca2+ mobilization, which is coupled to apical exocytotic insertion of aquaporin-2. Vasopressin-induced Ca2+ mobilization is in the form of oscillations, which involves both intracellular Ca2+ release from ryanodine-gated Ca2+ stores and extracellular Ca2+ influx via capacitative calcium entry. Each individual cell operates as an independent calcium oscillator with time variance in frequency and amplitude. Vasopressin-induced Ca2+ mobilization is mediated by cAMP, but is independent of PKA. Exogenous cAMP analog (8-pCPT-2′-O-Me-cAMP), which activates Epac (exchange protein directly activated by cAMP), but not PKA, triggers Ca2+ mobilization and apical exocytosis. These observations suggest that activation of Epac by cAMP may also contribute to the action of vasopressin in regulating osmotic water permeability. There are multiple plausible candidates for downstream effectors of vasopressin-induced Ca2+ signal including calmodulin, myosin light chain kinase, calmodulin kinase II, and calcineurin. All of them have been implicated in the regulation of aquaporin-2 trafficking and/or water permeability.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Agre P, Bonhivers M, Borgnia MJ (1998) The aquaporins, blueprints for cellular plumbing systems. J Biol Chem 273:14659–14662

    Article  PubMed  CAS  Google Scholar 

  2. Aromolaran AA, Blatter LA (2005) Modulation of intracellular Ca2+ release and capacitative Ca2+ entry by CaMKII inhibitors in bovine vascular endothelial cells. Am J Physiol Cell Physiol 289:C1426–C1436

    Article  PubMed  CAS  Google Scholar 

  3. Berridge MJ (1997) Elementary and global aspects of calcium signalling. J Exp Biol 200:315–319

    PubMed  CAS  Google Scholar 

  4. Bos JL (2003) Epac: a new cAMP target and new avenues in cAMP research. Nat Rev Mol Cell Biol 4:733–738

    Article  PubMed  CAS  Google Scholar 

  5. Brown D, Katsura T, Gustafson CE (1998) Cellular mechanisms of aquaporin trafficking. Am J Physiol 275:F328–F331

    PubMed  CAS  Google Scholar 

  6. Burgoyne RD, Morgan A (1998) Calcium sensors in regulated exocytosis. Cell Calcium 24:367–376

    Article  PubMed  CAS  Google Scholar 

  7. Chabardes D, Firsov D, Aarab L, Clabecq A, Bellanger AC, Siaume-Perez S, Elalouf JM (1996) Localization of mRNAs encoding Ca2+-inhibitable adenylyl cyclases along the renal tubule. Functional consequences for regulation of the cAMP content. J Biol Chem 271:19264–19271

    Article  PubMed  CAS  Google Scholar 

  8. Chou CL, Rapko SI, Knepper MA (1998) Phosphoinositide signaling in rat inner medullary collecting duct. Am J Physiol 274:F564–F572

    PubMed  CAS  Google Scholar 

  9. Chou CL, Yip KP, Knepper MA (1999) Role of Ca/Calmodulin in vasopressin-stimulated aquaporin-2 trafficking in rat collecting duct. J Am Soc Nephrol 10:13A

    Google Scholar 

  10. Chou CL, Yip KP, Michea L, Kador K, Ferraris JD, Wade JB, Knepper MA (2000) Regulation of aquaporin-2 trafficking by vasopressin in the renal collecting duct. Roles of ryanodine-sensitive Ca2+ stores and calmodulin. J Biol Chem 275:36839–36846

    Article  PubMed  CAS  Google Scholar 

  11. Chou CL, Lanerolle PD, Knepper MA (2001) Roles of actin, myosin and myosin light chain kinase in aquaporin-2 (AQP-2) trafficking. J Am Soc Nephrol 12:14A

    Article  Google Scholar 

  12. Chou CL, Christensen BM, Frische S, Vorum H, Desai RA, Hoffert JD, de Lanerolle P, Nielsen S, Knepper MA (2004) Non-muscle myosin II and myosin light chain kinase are downstream targets for vasopressin signaling in the renal collecting duct. J Biol Chem 279:49026–49035

    Article  PubMed  CAS  Google Scholar 

  13. Christensen AE, Selheim F, de Rooij J, Dremier S, Schwede F, Dao KK, Martinez A, Maenhaut C, Bos JL, Genieser HG, Doskeland SO (2003) cAMP analog mapping of Epac1 and cAMP kinase. Discriminating analogs demonstrate that Epac and cAMP kinase act synergistically to promote PC-12 cell neurite extension. J Biol Chem 278:35394–35402

    Article  PubMed  CAS  Google Scholar 

  14. Cochilla AJ, Angleson JK, Betz WJ (1999) Monitoring secretory membrane with FM1-43 fluorescence. Annu Rev Neurosci 22:1–10

    Article  PubMed  CAS  Google Scholar 

  15. Cooper DM, Yoshimura M, Zhang Y, Chiono M, Mahey R (1994) Capacitative Ca2+ entry regulates Ca(2+)-sensitive adenylyl cyclases. Biochem J 297(Pt 3):437–440

    PubMed  CAS  Google Scholar 

  16. De Koninck P, Schulman H (1998) Sensitivity of CaM kinase II to the frequency of Ca2+ oscillations [see comments]. Science 279:227–230

    Article  PubMed  Google Scholar 

  17. de Rooij J, Zwartkruis FJ, Verheijen MH, Cool RH, Nijman SM, Wittinghofer A, Bos JL (1998) Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP. Nature 396:474–477

    Article  PubMed  CAS  Google Scholar 

  18. Defer N, Best-Belpomme M, Hanoune J (2000) Tissue specificity and physiological relevance of various isoforms of adenylyl cyclase. Am J Physiol Renal Physiol 279:F400–F416

    PubMed  CAS  Google Scholar 

  19. Ecelbarger CA, Chou CL, Lolait SJ, Knepper MA, DiGiovanni SR (1996) Evidence for dual signaling pathways for V2 vasopressin receptor in rat inner medullary collecting duct. Am J Physiol 270:F623–F633

    PubMed  CAS  Google Scholar 

  20. Fushimi K, Uchida S, Hara Y, Hirata Y, Marumo F, Sasaki S (1993) Cloning and expression of apical membrane water channel of rat kidney collecting tubule. Nature 361:549–552

    Article  PubMed  CAS  Google Scholar 

  21. Gooch JL, Pergola PE, Guler RL, Abboud HE, Barnes JL (2004) Differential expression of calcineurin A isoforms in the diabetic kidney. J Am Soc Nephrol 15:1421–1429

    Article  PubMed  CAS  Google Scholar 

  22. Gooch JL (2006) An emerging role for calcineurin Aalpha in the development and function of the kidney. Am J Physiol Renal Physiol 290:F769–F776

    Article  PubMed  CAS  Google Scholar 

  23. Gooch JL, Guler RL, Barnes JL, Toro JJ (2006) Loss of calcineurin Aalpha results in altered trafficking of AQP2 and in nephrogenic diabetes insipidus. J Cell Sci 119:2468–2476

    Article  PubMed  CAS  Google Scholar 

  24. Gouraud S, Laera A, Calamita G, Rossetto O, Montecucco C, Rosenthal W, Svelto M, Valenti G (2001) Functional involvement of the SNARE machinery in cAMP-induced aquaporin-2 targetting to the apical plasma membrane. J Am Soc Nephrol 12:57A

    Article  Google Scholar 

  25. Gunnarson E, Zelenina M, Aperia A (2004) Regulation of brain aquaporins. Neuroscience 129:947–955

    Article  PubMed  CAS  Google Scholar 

  26. Gunnarson E, Axehult G, Baturina G, Zelenin S, Zelenina M, Aperia A (2005) Lead induces increased water permeability in astrocytes expressing aquaporin 4. Neuroscience 136:105–114

    Article  PubMed  CAS  Google Scholar 

  27. Hidaka H, Kobayashi R (1992) Pharmacology of protein kinase inhibitors. Annu Rev Pharmacol Toxicol 32:377–397

    Article  PubMed  CAS  Google Scholar 

  28. Hoffert JD, Chou CL, Fenton RA, Knepper MA (2005) Calmodulin is required for vasopressin-stimulated increase in cyclic AMP production in inner medullary collecting duct. J Biol Chem 280:13624–13630

    Article  PubMed  CAS  Google Scholar 

  29. Holz GG, Kang G, Harbeck M, Roe MW, Chepurny OG (2006) Cell physiology of cAMP sensor Epac. J Physiol 577:5–15

    Article  PubMed  CAS  Google Scholar 

  30. Honegger KJ, Capuano P, Winter C, Bacic D, Stange G, Wagner CA, Biber J, Murer H, Hernando N (2006) Regulation of sodium-proton exchanger isoform 3 (NHE3) by PKA and exchange protein directly activated by cAMP (EPAC). Proc Natl Acad Sci USA 103:803–808

    Article  PubMed  CAS  Google Scholar 

  31. Jo I, Ward DT, Baum MA, Scott JD, Coghlan VM, Hammond TG, Harris HW (2001) AQP2 is a substrate for endogenous PP2B activity within an inner medullary AKAP-signaling complex. Am J Physiol Renal Physiol 281:F958–F965

    PubMed  CAS  Google Scholar 

  32. Kang G, Chepurny OG, Holz GG (2001) cAMP-regulated guanine nucleotide exchange factor II (Epac2) mediates Ca2+-induced Ca2+ release in INS-1 pancreatic beta-cells. J Physiol 536:375–385

    Article  PubMed  CAS  Google Scholar 

  33. Kang G, Joseph JW, Chepurny OG, Monaco M, Wheeler MB, Bos JL, Schwede F, Genieser HG, Holz GG (2003) Epac-selective cAMP analog 8-pCPT-2’-O-Me-cAMP as a stimulus for Ca2+-induced Ca2+ release and exocytosis in pancreatic beta-cells. J Biol Chem 278:8279–8285

    Article  PubMed  CAS  Google Scholar 

  34. Kang G, Chepurny OG, Rindler MJ, Collis L, Chepurny Z, Li WH, Harbeck M, Roe MW, Holz GG (2005) A cAMP and Ca2+ coincidence detector in support of Ca2+-induced Ca2+ release in mouse pancreatic beta cells. J Physiol 566:173–188

    Article  PubMed  CAS  Google Scholar 

  35. Kang G, Chepurny OG, Malester B, Rindler MJ, Rehmann H, Bos JL, Schwede F, Coetzee WA, Holz GG (2006) cAMP sensor Epac as a determinant of ATP-sensitive potassium channel activity in human pancreatic beta cells and rat INS-1 cells. J Physiol 573:595–609

    Article  PubMed  CAS  Google Scholar 

  36. Kashima Y, Miki T, Shibasaki T, Ozaki N, Miyazaki M, Yano H, Seino S (2001) Critical role of cAMP-GEFII-Rim2 complex in incretin-potentiated insulin secretion. J Biol Chem 276:46046–46053

    Article  PubMed  CAS  Google Scholar 

  37. Katsura T, Gustafson CE, Ausiello DA, Brown D (1997) Protein kinase A phosphorylation is involved in regulated exocytosis of aquaporin-2 in transfected LLC-PK1 cells. Am J Physiol 272:F817–F822

    PubMed  CAS  Google Scholar 

  38. Katsushika S, Chen L, Kawabe J, Nilakantan R, Halnon NJ, Homcy CJ, Ishikawa Y (1992) Cloning and characterization of a sixth adenylyl cyclase isoform: types V and VI constitute a subgroup within the mammalian adenylyl cyclase family. Proc Natl Acad Sci USA 89:8774–8778

    Article  PubMed  CAS  Google Scholar 

  39. Kawasaki H, Springett GM, Mochizuki N, Toki S, Nakaya M, Matsuda M, Housman DE, Graybiel AM (1998) A family of cAMP-binding proteins that directly activate Rap1. Science 282:2275–2279

    Article  PubMed  CAS  Google Scholar 

  40. Knepper MA (1997) Molecular physiology of urinary concentrating mechanism: regulation of aquaporin water channels by vasopressin. Am J Physiol 272:F3–F12

    PubMed  CAS  Google Scholar 

  41. Laroche-Joubert N, Marsy S, Michelet S, Imbert-Teboul M, Doucet A (2002) Protein kinase A-independent activation of ERK and H,K-ATPase by cAMP in native kidney cells: role of Epac I. J Biol Chem 277:18598–18604

    Article  PubMed  CAS  Google Scholar 

  42. Lorenz D, Krylov A, Hahm D, Hagen V, Rosenthal W, Pohl P, Maric K (2003) Cyclic AMP is sufficient for triggering the exocytic recruitment of aquaporin-2 in renal epithelial cells. EMBO Rep 4:88–93

    Article  PubMed  CAS  Google Scholar 

  43. Nielsen S, Chou CL, Marples D, Christensen EI, Kishore BK, Knepper MA (1995) Vasopressin increases water permeability of kidney collecting duct by inducing translocation of aquaporin-CD water channels to plasma membrane. Proc Natl Acad Sci USA 92:1013–1017

    Article  PubMed  CAS  Google Scholar 

  44. Nielsen S, Frokiaer J, Marples D, Kwon TH, Agre P, Knepper MA (2002) Aquaporins in the kidney: from molecules to medicine. Physiol Rev 82:205–244

    PubMed  CAS  Google Scholar 

  45. Nishimoto G, Zelenina M, Li D, Yasui M, Aperia A, Nielsen S, Nairn AC (1999) Arginine vasopressin stimulates phosphorylation of aquaporin-2 in rat renal tissue. Am J Physiol 276:F254–F259

    PubMed  CAS  Google Scholar 

  46. Noda Y, Horikawa S, Katayama Y, Sasaki S (2004) Water channel aquaporin-2 directly binds to actin. Biochem Biophys Res Commun 322:740–745

    Article  PubMed  CAS  Google Scholar 

  47. Ozaki N, Shibasaki T, Kashima Y, Miki T, Takahashi K, Ueno H, Sunaga Y, Yano H, Matsuura Y, Iwanaga T, Takai Y, Seino S (2000) cAMP-GEFII is a direct target of cAMP in regulated exocytosis. Nat Cell Biol 2:805–811

    Article  PubMed  CAS  Google Scholar 

  48. Pabelick CM, Sieck GC, Prakash YS (2001) Invited review: significance of spatial and temporal heterogeneity of calcium transients in smooth muscle. J Appl Physiol 91:488–496

    PubMed  CAS  Google Scholar 

  49. Procino G, Carmosino M, Marin O, Brunati AM, Contri A, Pinna LA, Mannucci R, Nielsen S, Kwon TH, Svelto M, Valenti G (2003) Ser-256 phosphorylation dynamics of aquaporin 2 during maturation from the ER to the vesicular compartment in renal cells. FASEB J 17:1886–1888

    PubMed  CAS  Google Scholar 

  50. Putney JW Jr (1997) Type 3 inositol 1,4,5-trisphosphate receptor and capacitative calcium entry. Cell Calcium 21:257–261

    Article  PubMed  CAS  Google Scholar 

  51. Raghavan R, Chen X, Yip KP, Marsh DJ, Chon KH (2006) Interactions between TGF-dependent and myogenic oscillations in tubular pressure and whole kidney blood flow in both SDR and SHR. Am J Physiol Renal Physiol 290:F720–F732

    Article  PubMed  CAS  Google Scholar 

  52. Renstrom E, Eliasson L, Rorsman P (1997) Protein kinase A-dependent and -independent stimulation of exocytosis by cAMP in mouse pancreatic B-cells. J Physiol 502:105–118

    Article  PubMed  CAS  Google Scholar 

  53. Seino S, Shibasaki T (2005) PKA-dependent and PKA-independent pathways for cAMP-regulated exocytosis. Physiol Rev 85:1303–1342

    Article  PubMed  CAS  Google Scholar 

  54. Smith CB, Betz WJ (1996) Simultaneous independent measurement of endocytosis and exocytosis. Nature 380:531–534

    Article  PubMed  CAS  Google Scholar 

  55. Snyder HM, Noland TD, Breyer MD (1992) cAMP-dependent protein kinase mediates hydrosmotic effect of vasopressin in collecting duct. Am J Physiol 263:C147–C153

    PubMed  CAS  Google Scholar 

  56. Soderling TR, Stull JT (2001) Structure and regulation of calcium/calmodulin-dependent protein kinases. Chem Rev 101:2341–2352

    Article  PubMed  CAS  Google Scholar 

  57. Star RA, Nonoguchi H, Balaban R, Knepper MA (1988) Calcium and cyclic adenosine monophosphate as second messengers for vasopressin in the rat inner medullary collecting duct. J Clin Invest 81:1879–1888

    Article  PubMed  CAS  Google Scholar 

  58. Takahashi N, Kishimoto T, Nemoto T, Kadowaki T, Kasai H (2002) Fusion pore dynamics and insulin granule exocytosis in the pancreatic islet. Science 297:1349–1352

    Article  PubMed  CAS  Google Scholar 

  59. Tse A, Tse FW, Almers W, Hille B (1993) Rhythmic exocytosis stimulated by GnRH-induced calcium oscillations in rat gonadotropes. Science 260:82–84

    Article  PubMed  CAS  Google Scholar 

  60. Umenishi F, Verbavatz JM, Verkman AS (2000) cAMP regulated membrane diffusion of a green fluorescent protein-aquaporin 2 chimera. Biophys J 78:1024–1035

    Article  PubMed  CAS  Google Scholar 

  61. Wade JB, Stetson DL, Lewis SA (1981) ADH action: evidence for a membrane shuttle mechanism. Ann N Y Acad Sci 372:106–117

    Article  PubMed  CAS  Google Scholar 

  62. Wall SM, Han JS, Chou CL, Knepper MA (1992) Kinetics of urea and water permeability activation by vasopressin in rat terminal IMCD. Am J Physiol 262:F989–F998

    PubMed  CAS  Google Scholar 

  63. Xia SL, Wingo CS (2001) Calcium entry into mouse IMCD-3 cells by ATP can be regulated by ryanodine-sensitive calcium stores. J Am Soc Nephrol 12:603A

    Google Scholar 

  64. Yamamoto T, Sasaki S, Fushimi K, Ishibashi K, Yaoita E, Kawasaki K, Marumo F, Kihara I (1995) Vasopressin increases AQP-CD water channel in apical membrane of collecting duct cells in Brattleboro rats. Am J Physiol 268:C1546–C1551

    PubMed  CAS  Google Scholar 

  65. Yip KP (2002) Coupling of vasopressin-induced intracellular Ca2+ mobilization and apical exocytosis in perfused rat kidney collecting duct. J Physiol 538:891–899

    Article  PubMed  CAS  Google Scholar 

  66. Yip KP (2006) Epac-mediated Ca2+ mobilization and exocytosis in inner medullary collecting duct. Am J Physiol Renal Physiol 291:F882–F890

    Article  PubMed  CAS  Google Scholar 

  67. Zelenina M, Brismar H (2000) Osmotic water permeability measurements using confocal laser scanning microscopy. Eur Biophys J 29:165–171

    Article  PubMed  CAS  Google Scholar 

  68. Zhang M, Yuan T (1998) Molecular mechanisms of calmodulin’s functional versatility. Biochem Cell Biol 76:313–323

    Article  PubMed  CAS  Google Scholar 

  69. Zou R, Cupples WA, Yip KP, Holstein-Rathlou NH, Chon KH (2002) Time-varying properties of renal autoregulatory mechanisms. IEEE Trans Biomed Eng 49:1112–1120

    Article  PubMed  Google Scholar 

Download references

Acknowledgments

The authors acknowledge Drs. C.-L. Chou, M.A. Knepper and D.J. Marsh for their helpful suggestion. This study was supported by NIH Grant DK-60501 and a grant-in-aid from the American Heart Association, Florida Affiliate.

Author information

Authors and Affiliations

  1. Department of Molecular Pharmacology and Physiology, College of Medicine, University of South Florida, MDC 8, 12901 Bruce B. Downs Boulevard, Tampa, FL, 33612, USA

    Lavanya Balasubramanian & Kay-Pong Yip

  2. Division of Pulmonary and Critical Care Medicine, Johns Hopkins School of Medicine, Baltimore, MD, USA

    James S. K. Sham

Authors
  1. Lavanya Balasubramanian
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. James S. K. Sham
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Kay-Pong Yip
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Kay-Pong Yip.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Balasubramanian, L., Sham, J.S.K. & Yip, KP. Calcium signaling in vasopressin-induced aquaporin-2 trafficking. Pflugers Arch - Eur J Physiol 456, 747–754 (2008). https://doi.org/10.1007/s00424-007-0371-7

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00424-007-0371-7

Keywords

Search

Navigation