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

J. Biol. Chem., Vol. 283, Issue 10, 6476-6488, March 7, 2008

This Article Full Text Full Text (PDF) Supplemental Data All Versions of this Article: 283/10/6476    most recent M708776200v1 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 Hernández-Deviez, D. J. Articles by Parton, R. G. Search for Related Content PubMed PubMed Citation Articles by Hernández-Deviez, D. J. Articles by Parton, R. G. Social Bookmarking                      What's this?

Caveolin Regulates Endocytosis of the Muscle Repair Protein, Dysferlin^*

Delia J. Hernández-Deviez, Mark T. Howes, Steven H. Laval, Kate Bushby, John F. Hancock, and Robert G. Parton^¶1

From the Institute for Molecular Bioscience, ^¶Centre for Microscopy and Microanalysis, University of Queensland, Brisbane, Queensland 4072, Australia and the Institute of Human Genetics, International, Centre for Life, Newcastle NE1 3BZ, United Kingdom

Dysferlin and Caveolin-3 are plasma membrane proteins associated with muscular dystrophy. Patients with mutations in the CAV3 gene show dysferlin mislocalization in muscle cells. By utilizing caveolin-null cells, expression of caveolin mutants, and different mutants of dysferlin, we have dissected the site of action of caveolin with respect to dysferlin trafficking pathways. We now show that Caveolin-1 or -3 can facilitate exit of a dysferlin mutant that accumulates in the Golgi complex of Cav1^-/- cells. In contrast, wild type dysferlin reaches the plasma membrane but is rapidly endocytosed in Cav1^-/- cells. We demonstrate that the primary effect of caveolin is to cause surface retention of dysferlin. Caveolin-1 or Caveolin-3, but not specific caveolin mutants, inhibit endocytosis of dysferlin through a clathrin-independent pathway colocalizing with internalized glycosylphosphatidylinositol-anchored proteins. Our results provide new insights into the role of this endocytic pathway in surface remodeling of specific surface components. In addition, they highlight a novel mechanism of action of caveolins relevant to the pathogenic mechanisms underlying caveolin-associated disease.

Received for publication, October 24, 2007 , and in revised form, November 26, 2007.

^* This work was supported by grants from the National Health and Medical Research Council of Australia (to R. G. P. and J. F. H.), the Muscular Dystrophy Campaign, Association Francais contre les Myopathies, and the Jain Foundation (to K. B. and S. H. L.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

The on-line version of this article (available at http://www.jbc.org) contains supplemental Figs. S1 and S2.

¹ To whom correspondence should be addressed: Institute for Molecular Bioscience, University of Queensland, Brisbane QLD 4072, Australia. Tel.: 61-7-3346-2032; Fax: 61-7-3346-2339; E-mail: R.Parton{at}imb.uq.edu.au.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				C. Cai, N. Weisleder, J.-K. Ko, S. Komazaki, Y. Sunada, M. Nishi, H. Takeshima, and J. Ma Membrane Repair Defects in Muscular Dystrophy Are Linked to Altered Interaction between MG53, Caveolin-3, and Dysferlin J. Biol. Chem., June 5, 2009; 284(23): 15894 - 15902. [Abstract] [Full Text] [PDF]

				Y.-H. Chiu, M. A. Hornsey, L. Klinge, L. H. Jorgensen, S. H. Laval, R. Charlton, R. Barresi, V. Straub, H. Lochmuller, and K. Bushby Attenuated muscle regeneration is a key factor in dysferlin-deficient muscular dystrophy Hum. Mol. Genet., June 1, 2009; 18(11): 1976 - 1989. [Abstract] [Full Text] [PDF]

				P. Lajoie, J. G. Goetz, J. W. Dennis, and I. R. Nabi Lattices, rafts, and scaffolds: domain regulation of receptor signaling at the plasma membrane J. Cell Biol., May 4, 2009; 185(3): 381 - 385. [Abstract] [Full Text] [PDF]

				M Filosto, P Tonin, G Vattemi, M Scarpelli, C Baronchelli, L Broglio, M Tentorio, M Cotelli, A Padovani, and G Tomelleri Chronic ophthalmoparesis in limb girdle muscular dystrophy 1C J. Neurol. Neurosurg. Psychiatry, April 1, 2009; 80(4): 448 - 449. [Full Text] [PDF]

				M. S. Steen, M. E. Adams, Y. Tesch, and S. C. Froehner Amelioration of Muscular Dystrophy by Transgenic Expression of Niemann-Pick C1 Mol. Biol. Cell, January 1, 2009; 20(1): 146 - 152. [Abstract] [Full Text] [PDF]

				O. L. Gervasio, N. P. Whitehead, E. W. Yeung, W. D. Phillips, and D. G. Allen TRPC1 binds to caveolin-3 and is regulated by Src kinase - role in Duchenne muscular dystrophy J. Cell Sci., July 1, 2008; 121(13): 2246 - 2255. [Abstract] [Full Text] [PDF]