CPNA-1, a copine domain protein, is located at integrin adhesion sites and is required for myofilament stability in Caenorhabditis elegans

• Type of Material: Article
• Authors: Adam Warner, University of British Columbia; Ge Xiong, Emory University; Hiroshi Qadota, Emory University; Teresa Rogalski, University of British Columbia; A. Wayne Vogl, University of British Columbia; Donald G. Moerman, University of British Columbia; Guy Benian, Emory University
• Language: English
• Date: 2013-03-01
• Publisher: American Society for Cell Biology
• Publication Version: Final Published Version
• Copyright Statement: © 2013 Warner et al. This article is distributed by The American Society for Cell Biology under license from the author(s).
• License: Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported
• Final Published Version (URL): http://www.molbiolcell.org/content/24/5/601
• Title of Journal or Parent Work: Molecular Biology of the Cell
• ISSN: 1059-1524
• Volume: 24
• Issue: 5
• Start Page: 601
• End Page: 616
• Grant/Funding Information: D.G.M. thanks the Canadian Institute for Health Research and the National Science and Engineering Research Council of Canada for current support.; G.M.B. thanks the Department of Pathology, Emory University, for current support, and the National Institutes of Health for previous support (Grants AR051466 and AR052133).
• Research Categories: Health Sciences, Pathology; Biology, Molecular

Abstract

ABSTRACT: We identify cpna-1 (F31D5.3) as a novel essential muscle gene in the nematode Caenorhabditis elegans. Antibodies specific to copine domain protein atypical-1 (CPNA-1), as well as a yellow fluorescent protein translational fusion, are localized to integrin attachment sites (M-lines and dense bodies) in the body-wall muscle of C. elegans. CPNA-1 contains an N-terminal predicted transmembrane domain and a C-terminal copine domain and binds to the M-line/dense body protein PAT-6 (actopaxin) and the M-line proteins UNC-89 (obscurin), LIM-9 (FHL), SCPL-1 (SCP), and UNC-96. Proper CPNA-1 localization is dependent upon PAT-6 in embryonic and adult muscle. Nematodes lacking cpna-1 arrest elongation at the twofold stage of embryogenesis and display disruption of the myofilament lattice. The thick-filament component myosin heavy chain MYO-3 and the M-line component UNC-89 are initially localized properly in cpna-1–null embryos. However, in these embryos, when contraction begins, MYO-3 and UNC-89 become mislocalized into large foci and animals die. We propose that CPNA-1 acts as a linker between an integrin-associated protein, PAT-6, and membrane-distal components of integrin adhesion complexes in the muscle of C. elegans.