title: CPNA-1, a copine domain protein, is located at integrin adhesion sites and is required for myofilament stability in Caenorhabditis elegans.
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.
authors.affiliation: Department of Zoology, University of British Columbia, Vancouver, BC V6T 1Z4, Canada.
authors.forename: Adam
authors.initials: A
authors.lastname: Warner
authors.forename: Ge
authors.initials: G
authors.lastname: Xiong
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Qadota
authors.forename: Teresa
authors.initials: T
authors.lastname: Rogalski
authors.forename: A Wayne
authors.initials: AW
authors.lastname: Vogl
authors.forename: Donald G
authors.initials: DG
authors.lastname: Moerman
authors.forename: Guy M
authors.initials: GM
authors.lastname: Benian
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics / Q000254:growth & development / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D018507:Gene Expression Regulation, Developmental; D016023:Integrins / Q000378:metabolism*; D024510:Muscle Development; D009132:Muscles / Q000378:metabolism; D009210:Myofibrils / Q000235:genetics* / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary
chemical_list: C583397:CPNA-1 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D016023:Integrins; C110203:copine