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Calpains mediate integrin attachment complex maintenance of adult muscle in Caenorhabditis elegans

Etheridge, T and Oczypok, EA and Lehmann, S and Fields, BD and Shephard, F and Jacobson, LA and Szewczyk, NJ (2012) Calpains mediate integrin attachment complex maintenance of adult muscle in Caenorhabditis elegans. PLoS Genetics, 8 (1). ISSN 1553-7390

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Two components of integrin containing attachment complexes, UNC-97/PINCH and UNC-112/MIG-2/Kindlin-2, were recently identified as negative regulators of muscle protein degradation and as having decreased mRNA levels in response to spaceflight. Integrin complexes transmit force between the inside and outside of muscle cells and signal changes in muscle size in response to force and, perhaps, disuse. We therefore investigated the effects of acute decreases in expression of the genes encoding these multi-protein complexes. We find that in fully developed adult Caenorhabditis elegans muscle, RNAi against genes encoding core, and peripheral, members of these complexes induces protein degradation, myofibrillar and mitochondrial dystrophies, and a movement defect. Genetic disruption of Z-line- or M-line-specific complex members is sufficient to induce these defects. We confirmed that defects occur in temperature-sensitive mutants for two of the genes: unc-52, which encodes the extra-cellular ligand Perlecan, and unc-112, which encodes the intracellular component Kindlin-2. These results demonstrate that integrin containing attachment complexes, as a whole, are required for proper maintenance of adult muscle. These defects, and collapse of arrayed attachment complexes into ball like structures, are blocked when DIM-1 levels are reduced. Degradation is also blocked by RNAi or drugs targeting calpains, implying that disruption of integrin containing complexes results in calpain activation. In wild-type animals, either during development or in adults, RNAi against calpain genes results in integrin muscle attachment disruptions and consequent sub-cellular defects. These results demonstrate that calpains are required for proper assembly and maintenance of integrin attachment complexes. Taken together our data provide in vivo evidence that a calpain-based molecular repair mechanism exists for dealing with attachment complex disruption in adult muscle. Since C. elegans lacks satellite cells, this mechanism is intrinsic to the muscles and raises the question if such a mechanism also exists in higher metazoans. © 2012 Etheridge et al.


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Item Type: Article
Status: Published
CreatorsEmailPitt UsernameORCID
Etheridge, T
Lehmann, S
Fields, BD
Shephard, F
Jacobson, LAljac@pitt.eduLJAC0000-0002-0437-9375
Szewczyk, NJ
ContributionContributors NameEmailPitt UsernameORCID
Date: 1 January 2012
Date Type: Publication
Journal or Publication Title: PLoS Genetics
Volume: 8
Number: 1
DOI or Unique Handle: 10.1371/journal.pgen.1002471
Schools and Programs: Dietrich School of Arts and Sciences > Biological Sciences
Refereed: Yes
ISSN: 1553-7390
MeSH Headings: Animals; Caenorhabditis elegans--genetics; Caenorhabditis elegans--metabolism; Caenorhabditis elegans Proteins--metabolism; Calpain--antagonists & inhibitors; Calpain--metabolism; Cell Adhesion; Cell Adhesion Molecules--metabolism; Gene Expression Regulation; Gene Knockdown Techniques--methods; Immunoglobulins--metabolism; Integrins--chemistry; Integrins--metabolism; Membrane Proteins--metabolism; Mitochondria--metabolism; Multiprotein Complexes--chemistry; Multiprotein Complexes--metabolism; Muscle Cells--metabolism; Muscle Proteins--metabolism; Proteoglycans--metabolism; Proteolysis; RNA Interference
Other ID: NLM PMC3257289
PubMed Central ID: PMC3257289
PubMed ID: 22253611
Date Deposited: 13 Sep 2012 15:24
Last Modified: 07 May 2021 10:55


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