AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration Yanchao Huang * , Steven H. Laval † ,1 , Alexandra van Remoortere ‡ ,1 , Jacques Baudier § , Chriselle Benaud § , Louise V. B. Anderson † , Volker Straub † , Andre Deelder ‡ , Rune R. Frants * , Johan T. den Dunnen * , Kate Bushby † and Silvère M. van der Maarel * ,2 * Center for Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands; † Institute of Human Genetics, International Centre for Life, Newcastle-upon-Tyne, UK; ‡ Department of Parasitology, Leiden University Medical Center, Leiden, The Netherlands; and § INSERM EMI-104, DRDC CEA-Grenoble, France 2 Correspondence: Leiden Univesity Medical Center, Department of Human Genetics, Hlbinusdreef 2, 2333 ZA Leiden, The Netherlands. E-mail: maarel@lumc.nl 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.—Huang Y., Laval S. H., van Remoortere A., Baudier J., Benaud C., Anderson L. V. B., Straub V., Deelder A., Frants R. R., den Dunnen J. T., Bushby K., van der Maarel S. M. AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration. Key Words: protein interaction • dysferlinopathies • membrane repair • LGMD2B • MM
End of preview. The entire article is 11 pages. To view the full-text, please rent this article to continue.
/lp/fed-of-american-socs-for-experimental-biology/ahnak-a-novel-component-of-the-dysferlin-protein-complex-redistributes-osT2snHBAX
Welcome to DeepDyve! Rent Premier Research Articles and Save Up to 90%
AHNAK, a novel component of the dysferlin protein complex, redistributes to the cytoplasm with dysferlin during skeletal muscle regeneration
Huang, Yanchao; Laval, Steven H.; van Remoortere, Alexandra; Baudier, Jacques; Benaud, Chriselle; Anderson, Louise V. B.; Straub, Volker; Deelder, Andre; Frants, Rune R.; den Dunnen, Johan T.; Bushby, Kate; van der Maarel, Silvère M.
Follow The FASEB Journal
, Volume 21 (3): 732
Fed of American Socs for Experimental Biology – Mar 1, 2007
More Info
More Like This Article
View All dataSource[]=actageo&dataSource[]=aspet&dataSource[]=aaos&dataSource[]=aacc&dataSource[]=aacr&dataSource[]=aea&dataSource[]=aip&dataSource[]=ajnr&dataSource[]=ams&dataSource[]=aps_physical&dataSource[]=appi_book&dataSource[]=appi_journal&dataSource[]=apha&dataSource[]=asip&dataSource[]=asm&dataSource[]=asn&dataSource[]=aspb&dataSource[]=avs&dataSource[]=annual_reviews&dataSource[]=arxiv&dataSource[]=acm&dataSource[]=berghahn&dataSource[]=cabi&dataSource[]=clinical_trials&dataSource[]=dailymed&dataSource[]=degruyter&dataSource[]=du_press&dataSource[]=esa&dataSource[]=eu_press&dataSource[]=elsevier&dataSource[]=emerald&dataSource[]=ejtr&dataSource[]=emea&dataSource[]=epo&dataSource[]=faseb&dataSource[]=gsa&dataSource[]=health_affairs&dataSource[]=hindawi&dataSource[]=imanager&dataSource[]=imedpub&dataSource[]=informa_healthcare&dataSource[]=informs&dataSource[]=iop&dataSource[]=iucr&dataSource[]=iospress&dataSource[]=jbjs&dataSource[]=leftcoast&dataSource[]=lu_press&dataSource[]=mesharpe&dataSource[]=mary_ann_liebert&dataSource[]=medline&dataSource[]=mit_press&dataSource[]=nature&dataSource[]=oxford&dataSource[]=pier_professional&dataSource[]=pnas&dataSource[]=portlandpress&dataSource[]=psyc_articles&dataSource[]=psyc_books&dataSource[]=psyc_critiques&dataSource[]=plos_journal&dataSource[]=pubmed_central&dataSource[]=rsna&dataSource[]=rockefeller&dataSource[]=rcn&dataSource[]=ria&dataSource[]=rsc&dataSource[]=sage&dataSource[]=spie&dataSource[]=springer_journal&dataSource[]=springer&dataSource[]=taylor_francis&dataSource[]=aps&dataSource[]=the_scientist&dataSource[]=uc_press&dataSource[]=uspto_abstract&dataSource[]=wiley&dataSource[]=pct
© 2012 DeepDyve, Inc. All rights reserved.
Terms of Service | Privacy Policy
