HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 277, Issue 32, 28948-28958, August 9, 2002

This Article Full Text Full Text (PDF) All Versions of this Article: 277/32/28948    most recent M111706200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, H. Articles by Frizzell, R. A. Search for Related Content PubMed PubMed Citation Articles by Zhang, H. Articles by Frizzell, R. A. Social Bookmarking                      What's this?

Cysteine String Protein Interacts with and Modulates the Maturation of the Cystic Fibrosis Transmembrane Conductance Regulator^*

Hui Zhang, Kathryn W. Peters, Fei Sun, Christopher R. Marino, Jochen Lang^§, Robert D. Burgoyne^¶, and Raymond A. Frizzell

From the Department of Cell Biology and Physiology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15261, the  Department of Medicine, University of Tennessee, Memphis, Tennessee 38163, the ^§ Institut Européen de Chimie et Biologie, Pessac F-33607, France, and the ^¶ Physiological Laboratory, University of Liverpool, Liverpool L69 3BX, United Kingdom

The cystic fibrosis transmembrane conductance regulator (CFTR) is a cAMP-regulated chloride channel whose phosphorylation regulates both channel gating and its trafficking at the plasma membrane. Cysteine string proteins (Csps) are J-domain-containing, membrane-associated proteins that have been functionally implicated in regulated exocytosis. Therefore, we evaluated the possibility that Csp is involved in regulated CFTR trafficking. We found Csp expressed in mammalian epithelial cell lines, several of which express CFTR. In Calu-3 airway cells, immunofluorescence colocalized Csp with calnexin in the endoplasmic reticulum and with CFTR at the apical membrane domain. CFTR coprecipitated with Csp from Calu-3 cell lysates. Csp associated with both core-glycosylated immature and fully glycosylated mature CFTRs (bands B and C); however, in relation to the endogenous levels of the B and C bands expressed in Calu-3 cells, the Csp interaction with band B predominated. In vitro protein binding assays detected physical interactions of both mammalian Csp isoforms with the CFTR R-domain and the N terminus, having submicromolar affinities. In Xenopus oocytes expressing CFTR, Csp overexpression decreased the chloride current and membrane capacitance increases evoked by cAMP stimulation and decreased the levels of CFTR protein detected by immunoblot. In mammalian cells, the steady-state expression of CFTR band C was eliminated, and pulse-chase studies showed that Csp coexpression blocked the conversion of immature to mature CFTR and stabilized band B. These results demonstrate a primary role for Csp in CFTR protein maturation. The physical interaction of this Hsc70-binding protein with immature CFTR, its localization in the endoplasmic reticulum, and the decrease in production of mature CFTR observed during Csp overexpression reflect a role for Csp in CFTR biogenesis. The documented role of Csp in regulated exocytosis, its interaction with mature CFTR, and its coexpression with CFTR at the apical membrane domain of epithelial cells may reflect also a role for Csp in regulated CFTR trafficking at the plasma membrane.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				B. Z. Schmidt, R. J. Watts, M. Aridor, and R. A. Frizzell Cysteine String Protein Promotes Proteasomal Degradation of the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) by Increasing Its Interaction with the C Terminus of Hsp70-interacting Protein and Promoting CFTR Ubiquitylation J. Biol. Chem., February 13, 2009; 284(7): 4168 - 4178. [Abstract] [Full Text] [PDF]

				J. Park, S. Fang, A. L. Crews, K.-W. Lin, and K. B. Adler MARCKS Regulation of Mucin Secretion by Airway Epithelium in Vitro: Interaction with Chaperones Am. J. Respir. Cell Mol. Biol., July 1, 2008; 39(1): 68 - 76. [Abstract] [Full Text] [PDF]

				K. M. Bernardi, M. L. Forster, W. I. Lencer, and B. Tsai Derlin-1 Facilitates the Retro-Translocation of Cholera Toxin Mol. Biol. Cell, March 1, 2008; 19(3): 877 - 884. [Abstract] [Full Text] [PDF]

				W. H. Vila-Carriles, Z.-H. Zhou, J. K. Bubien, C. M. Fuller, and D. J. Benos Participation of the Chaperone Hsc70 in the Trafficking and Functional Expression of ASIC2 in Glioma Cells J. Biol. Chem., November 23, 2007; 282(47): 34381 - 34391. [Abstract] [Full Text] [PDF]

				H. A. J. Lu, T.-X. Sun, T. Matsuzaki, X.-H. Yi, J. Eswara, R. Bouley, M. McKee, and D. Brown Heat Shock Protein 70 Interacts with Aquaporin-2 and Regulates Its Trafficking J. Biol. Chem., September 28, 2007; 282(39): 28721 - 28732. [Abstract] [Full Text] [PDF]

				A. Ahner, K. Nakatsukasa, H. Zhang, R. A. Frizzell, and J. L. Brodsky Small Heat-Shock Proteins Select {Delta}F508-CFTR for Endoplasmic Reticulum-associated Degradation Mol. Biol. Cell, March 1, 2007; 18(3): 806 - 814. [Abstract] [Full Text] [PDF]

				J. Greaves and L. H. Chamberlain Dual Role of the Cysteine-String Domain in Membrane Binding and Palmitoylation-dependent Sorting of the Molecular Chaperone Cysteine-String Protein Mol. Biol. Cell, November 1, 2006; 17(11): 4748 - 4759. [Abstract] [Full Text] [PDF]

				K. Zaman, S. Carraro, J. Doherty, E. M. Henderson, E. Lendermon, L. Liu, G. Verghese, M. Zigler, M. Ross, E. Park, et al. S-Nitrosylating Agents: A Novel Class of Compounds That Increase Cystic Fibrosis Transmembrane Conductance Regulator Expression and Maturation in Epithelial Cells Mol. Pharmacol., October 1, 2006; 70(4): 1435 - 1442. [Abstract] [Full Text] [PDF]

				H. Zhang, B. Z. Schmidt, F. Sun, S. B. Condliffe, M. B. Butterworth, R. T. Youker, J. L. Brodsky, M. Aridor, and R. A. Frizzell Cysteine String Protein Monitors Late Steps in Cystic Fibrosis Transmembrane Conductance Regulator Biogenesis J. Biol. Chem., April 21, 2006; 281(16): 11312 - 11321. [Abstract] [Full Text] [PDF]

				J. Oberdorf, D. Pitonzo, and W. R. Skach An Energy-dependent Maturation Step Is Required for Release of the Cystic Fibrosis Transmembrane Conductance Regulator from Early Endoplasmic Reticulum Biosynthetic Machinery J. Biol. Chem., November 18, 2005; 280(46): 38193 - 38202. [Abstract] [Full Text] [PDF]

				C. M. Farinha and M. D. Amaral Most F508del-CFTR Is Targeted to Degradation at an Early Folding Checkpoint and Independently of Calnexin Mol. Cell. Biol., June 15, 2005; 25(12): 5242 - 5252. [Abstract] [Full Text] [PDF]

				X. Wang, J. Matteson, Y. An, B. Moyer, J.-S. Yoo, S. Bannykh, I. A. Wilson, J. R. Riordan, and W. E. Balch COPII-dependent export of cystic fibrosis transmembrane conductance regulator from the ER uses a di-acidic exit code J. Cell Biol., October 11, 2004; 167(1): 65 - 74. [Abstract] [Full Text] [PDF]

				W. B. Guggino and S. P. Banks-Schlegel Macromolecular Interactions and Ion Transport in Cystic Fibrosis Am. J. Respir. Crit. Care Med., October 1, 2004; 170(7): 815 - 820. [Abstract] [Full Text] [PDF]

				L. C. Miller, L. A. Swayne, J. G. Kay, Z.-P. Feng, S. E. Jarvis, G. W. Zamponi, and J. E. A. Braun Molecular determinants of cysteine string protein modulation of N-type calcium channels J. Cell Sci., July 15, 2003; 116(14): 2967 - 2974. [Abstract] [Full Text] [PDF]

				C. A. Bertrand and R. A. Frizzell The role of regulated CFTR trafficking in epithelial secretion Am J Physiol Cell Physiol, July 1, 2003; 285(1): C1 - C18. [Abstract] [Full Text] [PDF]

				S. B. Condliffe, M. D. Carattino, R. A. Frizzell, and H. Zhang Syntaxin 1A Regulates ENaC via Domain-specific Interactions J. Biol. Chem., April 4, 2003; 278(15): 12796 - 12804. [Abstract] [Full Text] [PDF]