Two components of integrin containing attachment complexes, @entity68621 /PINCH and @entity68622 / @entity68623 /Kindlin-2, were recently identified as negative regulators of muscle @entity1797 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 @entity2199 muscle, RNAi against genes encoding core, and peripheral, members of these complexes induces @entity1797 , myofibrillar and mitochondrial @entity3986 , and a @entity717 . 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: @entity37019 , which encodes the extra-cellular ligand Perlecan, and @entity68622 , 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 @entity68624 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 @entity2199 lacks satellite cells, this mechanism is intrinsic to the muscles and raises the question if such a mechanism also exists in higher metazoans.

Calpains mediate integrin attachment complex maintenance of adult muscle in XXXX .

@entity717 :: ('MESH:D009069', 'Disease') :: ['movement defect'] @entity2199 :: ('6239', 'Species') :: ['C. elegans', 'Caenorhabditis elegans'] @entity68624 :: ('181062(Tax:6239)', 'Gene') :: ['DIM-1'] @entity1797 :: ('MESH:D055959', 'Disease') :: ['protein degradation'] @entity3986 :: ('MESH:D009136', 'Disease') :: ['dystrophies'] @entity68623 :: ('181344(Tax:6239)', 'Gene') :: ['MIG-2'] @entity37019 :: ('175126(Tax:6239)', 'Gene') :: ['unc-52'] @entity68622 :: ('179972(Tax:6239)', 'Gene') :: ['unc-112', 'UNC-112'] @entity68621 :: ('180827(Tax:6239)', 'Gene') :: ['UNC-97']
@entity2199 :: (6239,Species) :: ['Caenorhabditis elegans']
