|
|
|
|||||||
|
|||||||||
J. Biol. Chem., Vol. 277, Issue 25, 22883-22888, June 21, 2002
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
From the Mutations in dysferlin, a novel membrane protein
of unknown function, lead to muscular dystrophy. Myoferlin is highly
homologous to dysferlin and like dysferlin is a plasma membrane protein
with six C2 domains highly expressed in muscle. C2 domains are found in
a variety of membrane-associated proteins where they have been implicated in calcium, phospholipid, and protein-binding. We
investigated the pattern of dysferlin and myoferlin expression in a
cell culture model of muscle development and found that dysferlin is
expressed in mature myotubes. In contrast, myoferlin is highly
expressed in elongated "prefusion" myoblasts and is decreased in
mature myotubes where dysferlin expression is greatest. We tested
ferlin C2 domains for their ability to bind phospholipid in a
calcium-sensitive manner. We found that C2A, the first C2 domain of
dysferlin and myoferlin, bound 50% phosphatidylserine and that
phospholipid binding was regulated by calcium concentration. A
dysferlin point mutation responsible for muscular dystrophy was
engineered into the dysferlin C2A domain and demonstrated reduced
calcium-sensitive phospholipid binding. Based on these data, we propose
a mechanism for muscular dystrophy in which calcium-regulated
phospholipid binding is abnormal, leading to defective maintenance and
repair of muscle membranes.
Calcium-sensitive Phospholipid Binding Properties of Normal and
Mutant Ferlin C2 Domains*
,
**
Department of Pathology, the
§ Department of Molecular Genetics and Cell Biology, the
¶ Department of Medicine, and the Department of Human
Genetics, The University of Chicago, Chicago, Illinois 60637
*
This work was supported by the Muscular Dystrophy
Association, the American Heart Association, and the National
Institutes of Health (to E. M. M.); a National Institutes of Health
Cardiovascular Pathophysiology training grant, an American Association
for University Women American dissertation fellowship, and the Medical
Scientist Training Program (to D. B. D.); and a National Science
Foundation fellowship (to K. R. D.).The costs of publication of this
article were defrayed in part by the
payment of page charges. The article must therefore be hereby marked
"advertisement" in
accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2002 by The American Society for Biochemistry and Molecular Biology, Inc.
CiteULike 
Complore 
Connotea 
Del.icio.us 
Digg 
Reddit 
Technorati What's this?
This article has been cited by other articles:
|
|
 |
|
  J. M. Robinson, W. E. Ackerman IV, N. J. Behrendt, and D. D. Vandre While Dysferlin and Myoferlin Are Coexpressed in the Human Placenta, Only Dysferlin Expression Is Responsive to Trophoblast Fusion in Model Systems Biol Reprod, July 1, 2009; 81(1): 33 - 39. [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]
|
|
|
|
 |
|
 R. V. Stahelin Lipid binding domains: more than simple lipid effectors J. Lipid Res., April 1, 2009; 50(Supplement): S299 - S304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Doherty, A. R. Demonbreun, G. Q. Wallace, A. Cave, A. D. Posey, K. Heretis, P. Pytel, and E. M. McNally The Endocytic Recycling Protein EHD2 Interacts with Myoferlin to Regulate Myoblast Fusion J. Biol. Chem., July 18, 2008; 283(29): 20252 - 20260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. D Vandre, W. E Ackerman IV, D. A Kniss, A. K Tewari, M. Mori, T. Takizawa, and J. M Robinson Dysferlin Is Expressed in Human Placenta But Does Not Associate with Caveolin Biol Reprod, September 1, 2007; 77(3): 533 - 542. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Klinge, S. Laval, S. Keers, F. Haldane, V. Straub, R. Barresi, and K. Bushby From T-tubule to sarcolemma: damage-induced dysferlin translocation in early myogenesis FASEB J, June 1, 2007; 21(8): 1768 - 1776. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Fujita, Y. Kouroku, A. Isoai, H. Kumagai, A. Misutani, C. Matsuda, Y. K. Hayashi, and T. Momoi Two endoplasmic reticulum-associated degradation (ERAD) systems for the novel variant of the mutant dysferlin: ubiquitin/proteasome ERAD(I) and autophagy/lysosome ERAD(II) Hum. Mol. Genet., March 15, 2007; 16(6): 618 - 629. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Huang, S. H. Laval, A. van Remoortere, J. Baudier, C. Benaud, L. V. B. Anderson, V. Straub, A. Deelder, R. R. Frants, J. T. den Dunnen, et al. AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration FASEB J, March 1, 2007; 21(3): 732 - 742. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. de Luna, E. Gallardo, M. Soriano, R. Dominguez-Perles, C. de la Torre, R. Rojas-Garcia, J. M. Garcia-Verdugo, and I. Illa Absence of Dysferlin Alters Myogenin Expression and Delays Human Muscle Differentiation "in Vitro" J. Biol. Chem., June 23, 2006; 281(25): 17092 - 17098. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. L. Washington and S. Ward FER-1 regulates Ca2+-mediated membrane fusion during C. elegans spermatogenesis J. Cell Sci., June 15, 2006; 119(12): 2552 - 2562. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. J. Vizeacoumar, W. N. Vreden, J. D. Aitchison, and R. A. Rachubinski Pex19p Binds Pex30p and Pex32p at Regions Required for Their Peroxisomal Localization but Separate from Their Peroxisomal Targeting Signals J. Biol. Chem., May 26, 2006; 281(21): 14805 - 14812. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. J. Hernandez-Deviez, S. Martin, S. H. Laval, H. P. Lo, S. T. Cooper, K. N. North, K. Bushby, and R. G. Parton Aberrant dysferlin trafficking in cells lacking caveolin or expressing dystrophy mutants of caveolin-3 Hum. Mol. Genet., January 1, 2006; 15(1): 129 - 142. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. R. Doherty, A. Cave, D. B. Davis, A. J. Delmonte, A. Posey, J. U. Earley, M. Hadhazy, and E. M. McNally Normal myoblast fusion requires myoferlin Development, December 15, 2005; 132(24): 5565 - 5575. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Irino, M. Ichinohe, Y. Nakamura, M. Nakahara, and K. Fukami Phospholipase C{delta}4 Associates with Glutamate Receptor Interacting Protein 1 in Testis J. Biochem., October 1, 2005; 138(4): 451 - 456. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Ho, C. M. Post, L. R. Donahue, H. G.W. Lidov, R. T. Bronson, H. Goolsby, S. C. Watkins, G. A. Cox, and R. H. Brown Jr Disruption of muscle membrane and phenotype divergence in two novel mouse models of dysferlin deficiency Hum. Mol. Genet., September 15, 2004; 13(18): 1999 - 2010. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Kirschner and C. G. Bonnemann The Congenital and Limb-Girdle Muscular Dystrophies: Sharpening the Focus, Blurring the Boundaries Arch Neurol, February 1, 2004; 61(2): 189 - 199. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Rico-Sanz, T. Rankinen, T. Rice, A. S. Leon, J. S. Skinner, J. H. Wilmore, D. C. Rao, and C. Bouchard Quantitative trait loci for maximal exercise capacity phenotypes and their responses to training in the HERITAGE Family Study Physiol Genomics, January 15, 2004; 16(2): 256 - 260. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. J. Lennon, A. Kho, B. J. Bacskai, S. L. Perlmutter, B. T. Hyman, and R. H. Brown Jr. Dysferlin Interacts with Annexins A1 and A2 and Mediates Sarcolemmal Wound-healing J. Biol. Chem., December 12, 2003; 278(50): 50466 - 50473. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Campanaro, C. Romualdi, M. Fanin, B. Celegato, B. Pacchioni, S. Trevisan, P. Laveder, C. De Pitta, E. Pegoraro, Y. K. Hayashi, et al. Gene expression profiling in dysferlinopathies using a dedicated muscle microarray Hum. Mol. Genet., December 15, 2002; 11(26): 3283 - 3298. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| All ASBMB Journals | Molecular and Cellular Proteomics |
| Journal of Lipid Research | ASBMB Today |