Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

Logo for

PNAS 103 (25): 9542-9547

Copyright © 2006 by the National Academy of Sciences.


BIOLOGICAL SCIENCES / CELL BIOLOGY

IRBIT, an inositol 1,4,5-trisphosphate receptor-binding protein, specifically binds to and activates pancreas-type Na+/HCO3 cotransporter 1 (pNBC1)

Kyoko Shirakabe*, Giuseppina Priori*, Hideomi Yamada{dagger}, Hideaki Ando{ddagger}, Shoko Horita{dagger}, Toshiro Fujita{dagger}, Ichiro Fujimoto*,§, Akihiro Mizutani, George Seki{dagger}, and Katsuhiko Mikoshiba*,{ddagger},§,||

Divisions of *Neural Signal Information NTT-IMSUT, and Molecular Neurobiology, Institute of Medical Science,University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639, Japan; {dagger}Department of Internal Medicine, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8635, Japan; {ddagger}Laboratory for Developmental Neurobiology, Brain Science Institute, The Institute of Physical and Chemical Research (RIKEN), 2-1 Hirosawa, Wako, Saitama 351-0198, Japan; and ||Calcium Oscillation Project, International Cooperative Research Project, Japan Science and Technology Corporation, 3-14-4 Shirokanedai, Minato-ku, Tokyo 108-0071, Japan

Edited by Solomon H. Snyder, Johns Hopkins University School of Medicine, Baltimore, MD, and approved May 8, 2006

Received for publication March 20, 2006.

Abstract: Inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are IP3-gated Ca2+ channels that are located on intracellular Ca2+ stores. We previously identified an IP3R binding protein, termed IP3R binding protein released with IP3 (IRBIT). Because IRBIT is released from IP3R by physiological concentrations of IP3, we hypothesized that IRBIT is a signaling molecule that is released from IP3R and regulates downstream target molecules in response to the production of IP3. Therefore, in this study, we attempted to identify the target molecules of IRBIT, and we succeeded in identifying Na+/HCO3 cotransporter 1 (NBC1) as an IRBIT binding protein. Of the two major splicing variants of NBC1, pancreas-type NBC1 (pNBC1) and kidney-type NBC1 (kNBC1), IRBIT was found to bind specifically to pNBC1 and not to bind to kNBC1. IRBIT binds to the N-terminal pNBC1-specific domain, and its binding depends on the phosphorylation of multiple serine residues of IRBIT. Also, an electrophysiological analysis in Xenopus oocytes revealed that pNBC1 requires coexpression of IRBIT to manifest substantial activity comparable with that of kNBC1, which displays substantial activity independently of IRBIT. These results strongly suggest that pNBC1 is the target molecule of IRBIT and that IRBIT has an important role in pH regulation through pNBC1. Also, our findings raise the possibility that the regulation through IRBIT enables NBC1 variants to have different physiological roles.

Key Words: pH • acidosis • phosphorylation


Author contributions: K.S., I.F., and K.M. designed research; K.S., G.P., H.Y., H.A., S.H., T.F., I.F., A.M., and G.S. performed research; and K.S. and G.S. wrote the paper.

Conflict of interest statement: No conflicts declared.

This paper was submitted directly (Track II) to the PNAS office.

§To whom correspondence may be addressed. E-mail: mikosiba{at}ims.u-tokyo.ac.jp or fujimoto{at}ims.u-tokyo.ac.jp

© 2006 by The National Academy of Sciences of the USA


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Effects of optional structural elements, including two alternative amino termini and a new splicing cassette IV, on the function of the sodium-bicarbonate cotransporter NBCn1 (SLC4A7).
Y. Liu, X. Qin, D.-K. Wang, Y.-M. Guo, H. S. Gill, N. Morris, M. D. Parker, L.-M. Chen, and W. F. Boron (2013)
J. Physiol. 591, 4983-5004
   Abstract »    Full Text »    PDF »
The Cystic Fibrosis of Exocrine Pancreas.
M. Wilschanski and I. Novak (2013)
Cold Spring Harb Perspect Med 3, a009746
   Abstract »    Full Text »    PDF »
The Divergence, Actions, Roles, and Relatives of Sodium-Coupled Bicarbonate Transporters.
M. D. Parker and W. F. Boron (2013)
Physiol Rev 93, 803-959
   Abstract »    Full Text »    PDF »
Convergence of IRBIT, phosphatidylinositol (4,5) bisphosphate, and WNK/SPAK kinases in regulation of the Na+-HCO3- cotransporters family.
J. H. Hong, D. Yang, N. Shcheynikov, E. Ohana, D. M. Shin, and S. Muallem (2013)
PNAS 110, 4105-4110
   Abstract »    Full Text »    PDF »
Chaperone Stress 70 Protein (STCH) Binds and Regulates Two Acid/Base Transporters NBCe1-B and NHE1.
J.-S. Bae, N.-Y. Koo, E. Namkoong, A. J. Davies, S.-K. Choi, Y. Shin, M. Jin, S.-M. Hwang, K. Mikoshiba, and K. Park (2013)
J. Biol. Chem. 288, 6295-6305
   Abstract »    Full Text »    PDF »
PIP2 hydrolysis stimulates the electrogenic Na+-bicarbonate cotransporter NBCe1-B and -C variants expressed in Xenopus laevis oocytes.
I. M. Thornell, J. Wu, X. Liu, and M. O. Bevensee (2012)
J. Physiol. 590, 5993-6011
   Abstract »    Full Text »    PDF »
The WNK/SPAK and IRBIT/PP1 Pathways in Epithelial Fluid and Electrolyte Transport.
S. Park, J. H. Hong, E. Ohana, and S. Muallem (2012)
Physiology 27, 291-299
   Abstract »    Full Text »    PDF »
Molecular Physiology of SPAK and OSR1: Two Ste20-Related Protein Kinases Regulating Ion Transport.
K. B. Gagnon and E. Delpire (2012)
Physiol Rev 92, 1577-1617
   Abstract »    Full Text »    PDF »
Transepithelial Bicarbonate Secretion: Lessons from the Pancreas.
H. W. Park and M. G. Lee (2012)
Cold Spring Harb Perspect Med 2, a009571
   Abstract »    Full Text »    PDF »
The role of aspartic acid residues 405 and 416 of the kidney isotype of sodium-bicarbonate cotransporter 1 in its targeting to the plasma membrane.
H. C. Li, V. Kucher, E. Y. Li, L. Conforti, K. A. Zahedi, and M. Soleimani (2012)
Am J Physiol Cell Physiol 302, C1713-C1730
   Abstract »    Full Text »    PDF »
Euryhaline pufferfish NBCe1 differs from nonmarine species NBCe1 physiology.
M.-H. Chang, C. Plata, Y. Kurita, A. Kato, S. Hirose, and M. F. Romero (2012)
Am J Physiol Cell Physiol 302, C1083-C1095
   Abstract »    Full Text »    PDF »
HCO3--independent conductance with a mutant Na+/HCO3- cotransporter (SLC4A4) in a case of proximal renal tubular acidosis with hypokalaemic paralysis.
M. D. Parker, X. Qin, R. C. Williamson, A. M. Toye, and W. F. Boron (2012)
J. Physiol. 590, 2009-2034
   Abstract »    Full Text »    PDF »
The Physiology of Bicarbonate Transporters in Mammalian Reproduction.
Y. Liu, D.-K. Wang, and L.-M. Chen (2012)
Biol Reprod 86, 99
   Abstract »    Full Text »    PDF »
Relief of autoinhibition of the electrogenic Na-HCO3 cotransporter NBCe1-B: role of IRBIT vs. amino-terminal truncation.
S.-K. Lee, W. F. Boron, and M. D. Parker (2012)
Am J Physiol Cell Physiol 302, C518-C526
   Abstract »    Full Text »    PDF »
Molecular Mechanism of Pancreatic and Salivary Gland Fluid and HCOFormula Secretion.
M. G. Lee, E. Ohana, H. W. Park, D. Yang, and S. Muallem (2012)
Physiol Rev 92, 39-74
   Abstract »    Full Text »    PDF »
Calcium Channels in the Development, Maturation, and Function of Spermatozoa.
A. Darszon, T. Nishigaki, C. Beltran, and C. L. Trevino (2011)
Physiol Rev 91, 1305-1355
   Abstract »    Full Text »    PDF »
Identification of a Potential Receptor That Couples Ion Transport to Protein Kinase Activity.
Q. Ye, Z. Li, J. Tian, J. X. Xie, L. Liu, and Z. Xie (2011)
J. Biol. Chem. 286, 6225-6232
   Abstract »    Full Text »    PDF »
Defective membrane expression of the Na+-HCO3- cotransporter NBCe1 is associated with familial migraine.
M. Suzuki, W. Van Paesschen, I. Stalmans, S. Horita, H. Yamada, B. A. Bergmans, E. Legius, F. Riant, P. De Jonghe, Y. Li, et al. (2010)
PNAS 107, 15963-15968
   Abstract »    Full Text »    PDF »
Activation of Na+/H+ Exchanger NHE3 by Angiotensin II Is Mediated by Inositol 1,4,5-Triphosphate (IP3) Receptor-binding Protein Released with IP3 (IRBIT) and Ca2+/Calmodulin-dependent Protein Kinase II.
P. He, J. Klein, and C. C. Yun (2010)
J. Biol. Chem. 285, 27869-27878
   Abstract »    Full Text »    PDF »
Cloning, localization, and functional expression of the electrogenic Na+ bicarbonate cotransporter (NBCe1) from zebrafish.
C. R. Sussman, J. Zhao, C. Plata, J. Lu, C. Daly, N. Angle, J. DiPiero, I. A. Drummond, J. O. Liang, W. F. Boron, et al. (2009)
Am J Physiol Cell Physiol 297, C865-C875
   Abstract »    Full Text »    PDF »
Phosphatidylinositol 4,5-bisphosphate (PIP2) stimulates the electrogenic Na/HCO3 cotransporter NBCe1-A expressed in Xenopus oocytes.
J. Wu, C. M. McNicholas, and M. O. Bevensee (2009)
PNAS 106, 14150-14155
   Abstract »    Full Text »    PDF »
Mutation of Aspartate 555 of the Sodium/Bicarbonate Transporter SLC4A4/NBCe1 Induces Chloride Transport.
H. S. Yang, E. Kim, S. Lee, H. J. Park, D. S. Cooper, I. Rajbhandari, and I. Choi (2009)
J. Biol. Chem. 284, 15970-15979
   Abstract »    Full Text »    PDF »
Modular structure of sodium-coupled bicarbonate transporters.
W. F. Boron, L. Chen, and M. D. Parker (2009)
J. Exp. Biol. 212, 1697-1706
   Abstract »    Full Text »    PDF »
Inositol 1,4,5-Triphosphate Receptor-binding Protein Released with Inositol 1,4,5-Triphosphate (IRBIT) Associates with Components of the mRNA 3' Processing Machinery in a Phosphorylation-dependent Manner and Inhibits Polyadenylation.
H. Kiefer, A. Mizutani, S.-I. Iemura, T. Natsume, H. Ando, Y. Kuroda, and K. Mikoshiba (2009)
J. Biol. Chem. 284, 10694-10705
   Abstract »    Full Text »    PDF »
IRBIT, Inositol 1,4,5-Triphosphate (IP3) Receptor-binding Protein Released with IP3, Binds Na+/H+ Exchanger NHE3 and Activates NHE3 Activity in Response to Calcium.
P. He, H. Zhang, and C. C. Yun (2008)
J. Biol. Chem. 283, 33544-33553
   Abstract »    Full Text »    PDF »
Cloning and characterization of novel human SLC4A8 gene products encoding Na+-driven Cl-/HCO3- exchanger variants NDCBE-A, -C, and -D.
M. D. Parker, P. Bouyer, C. M. Daly, and W. F. Boron (2008)
Physiol Genomics 34, 265-276
   Abstract »    Full Text »    PDF »
Entry to "Formula Tunnel" Revealed by SLC4A4 Human Mutation and Structural Model.
M.-H. Chang, J. DiPiero, F. D. Sonnichsen, and M. F. Romero (2008)
J. Biol. Chem. 283, 18402-18410
   Abstract »    Full Text »    PDF »
The electrogenicity of the rat sodium-bicarbonate cotransporter NBCe1 requires interactions among transmembrane segments of the transporter.
I. Choi, H. Soo Yang, and W. F. Boron (2007)
J. Physiol. 578, 131-142
   Abstract »    Full Text »    PDF »
The Inositol 1,4,5-Trisphosphate Receptor (IP3R) and Its Regulators: Sometimes Good and Sometimes Bad Teamwork.
C.-u. Choe and B. E. Ehrlich (2006)
Sci. STKE 2006, re15
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882