Dataset Information

Calpains promote ?2?1 integrin turnover in nonrecycling integrin pathway.

ABSTRACT: Collagen receptor integrins recycle between the plasma membrane and endosomes and facilitate formation and turnover of focal adhesions. In contrast, clustering of ?2?1 integrin with antibodies or the human pathogen echovirus 1 (EV1) causes redistribution of ?2 integrin to perinuclear multivesicular bodies, ?2-MVBs. We show here that the internalized clustered ?2 integrin remains in ?2-MVBs and is not recycled back to the plasma membrane. Instead, receptor clustering and internalization lead to an accelerated down-regulation of ?2?1 integrin compared to the slow turnover of unclustered ?2 integrin. EV1 infection or integrin degradation is not associated with proteasomal or autophagosomal processes and shows no significant association with lysosomal pathway. In contrast, degradation is dependent on calpains, such that it is blocked by calpain inhibitors. We show that active calpain is present in ?2-MVBs, internalized clustered ?2?1 integrin coprecipitates with calpain-1, and calpain enzymes can degrade ?2?1 integrin. In conclusion, we identified a novel virus- and clustering-specific pathway that diverts ?2?1 integrin from its normal endo/exocytic traffic to a nonrecycling, calpain-dependent degradative endosomal route.

SUBMITTER: Rintanen N

PROVIDER: S-EPMC3268724 | biostudies-literature | 2012 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway.

Rintanen Nina N Karjalainen Mikko M Alanko Jonna J Paavolainen Lassi L Mäki Anita A Nissinen Liisa L Lehkonen Moona M Kallio Katri K Cheng R Holland RH Upla Paula P Ivaska Johanna J Marjomäki Varpu V

Molecular biology of the cell 20111207 3

Collagen receptor integrins recycle between the plasma membrane and endosomes and facilitate formation and turnover of focal adhesions. In contrast, clustering of α2β1 integrin with antibodies or the human pathogen echovirus 1 (EV1) causes redistribution of α2 integrin to perinuclear multivesicular bodies, α2-MVBs. We show here that the internalized clustered α2 integrin remains in α2-MVBs and is not recycled back to the plasma membrane. Instead, receptor clustering and internalization lead to a ...[more]

PMID: 22160595

Similar Datasets

Project description: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.

Dataset Information

Calpains promote ?2?1 integrin turnover in nonrecycling integrin pathway.

Publications

Calpains promote α2β1 integrin turnover in nonrecycling integrin pathway.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets