Browse by author
Lookup NU author(s): Dr Steven Laval, Dr Louise VB Anderson, Professor Volker StraubORCiD, Emerita Professor Katherine Bushby
Full text for this publication is not currently held within this repository. Alternative links are provided below where available.
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. © FASEB.
Author(s): Huang Y, Laval SH, Van Remoortere A, Baudier J, Benaud C, Anderson LVB, Straub V, Deelder A, Frants RR, Den Dunnen JT, Bushby K, Van Der Maarel SM
Publication type: Article
Publication status: Published
Journal: FASEB Journal
Year: 2007
Volume: 21
Issue: 3
Pages: 732-742
Print publication date: 01/03/2007
ISSN (print): 0892-6638
ISSN (electronic): 1530-6860
Publisher: Federation of American Societies for Experimental Biology
URL: http://dx.doi.org/10.1096/fj.06-6628com
DOI: 10.1096/fj.06-6628com
PubMed id: 17185750
Altmetrics provided by Altmetric
