Ahnak, a Novel Component of the Dysferlin Protein Complex, Redistributes to the Cytoplasm with Dysferlin During Skeletal Muscle Regeneration.
From: Center for Human and Clinical Genetics, Leiden Univesity Medical Center, Leiden, The Netherlands.
The FASEB journal : official publication of the Federation of American Societies for Experimental Biology
- Publish Date: Mar 2007
- ISSN: 1530-6860
- Volume: 21
- Issue: 3
- Pages: 732-42
- Medium: Internet
- Language: English
- Citation (JAMA): Huang Yanchao, Laval Steven H, van Remoortere Alexandra, et al. Ahnak, a Novel Component of the Dysferlin Protein Complex, Redistributes to the Cytoplasm with Dysferlin During Skeletal Muscle Regeneration.. FASEB J. Mar 2007;21:732-42
Abstract
Mutations in dysferlin cause limb girdle muscular dystrophy 2B, Miyoshi myopathy and distal anterior compartment myopathy. Dysferlin is proposed to play a role in muscle membrane repair. To gain functional insight into the molecular mechanisms of dysferlin, we have searched for dysferlin-interacting proteins in skeletal muscle. By coimmunoprecipitation coupled with mass spectrometry, we demonstrate that AHNAK interacts with dysferlin. We defined the binding sites in dysferlin and AHNAK as the C2A domain in dysferlin and the carboxyterminal domain of AHNAK by glutathione S-transferase (GST)-pull down assays. As expected, the N-terminal domain of myoferlin also interacts with the carboxyterminal domain of AHNAK. In normal skeletal muscle, dysferlin and AHNAK colocalize at the sarcolemmal membrane and T-tubules. In dysferlinopathies, reduction or absence of dysferlin correlates with a secondary muscle-specific loss of AHNAK. Moreover, in regenerating rat muscle, dysferlin and AHNAK showed a marked increase and cytoplasmic localization, consistent with the direct interaction between them. Our data suggest that dysferlin participates in the recruitment and stabilization of AHNAK to the sarcolemma and that AHNAK plays a role in dysferlin membrane repair process. It may also have significant implications for understanding the biology of AHNAK-containing exocytotic vesicles, “enlargosomes,” in plasma membrane remodeling and repair.
Mesh Headings (Keywords): Animals, Carrier Proteins, Cytoplasm, Female, Humans, Immunoprecipitation, Mass Spectrometry, Membrane Proteins, Mice, Muscle Proteins, Muscle, Skeletal, Mutation, Neoplasm Proteins, Rats, Rats, Wistar, Regeneration
Check for Full Text / PubMed Unique Identifier (PMID): 17185750
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.