Kindlin-2 is required for myocyte elongation and is essential for myogenesis.
BACKGROUND
Integrins are required for normal muscle differentiation and disruptions in integrin signaling result in human muscle disease. The intracellular components that regulate integrin function during myogenesis are poorly understood. Unc-112 is an integrin-associated protein required for muscle development in C. elegans. To better understand the intracellular effectors of integrin signaling in muscle, we examined the mammalian homolog of Unc-112, kindlin-2.


RESULTS
Kindlin-2 expression is upregulated during differentiation and highly enriched at sites of integrin localization. RNAi knockdown of kindlin-2 in C2C12 cells results in significant abnormalities during the early stages of myogenesis. Specifically, differentiating myocytes lacking kindlin-2 are unable to elongate and fail to fuse into multinucleated myotubes. These changes are correlated with decreased cell substratum adhesion and increased cell motility. They are also associated with redistribution of a known kindlin-2 binding partner, integrin linked kinase (ILK), to the membrane insoluble subcellular fraction.


CONCLUSIONS
In all, our study reveals kindlin-2 as a novel integrin adaptor protein important for muscle differentiation, and identifies it particularly as a critical regulator of myocyte elongation.
Dowling
James J
JJ
Department of Pediatrics, University of Michigan, Ann Arbor, USA. jamedowl@umich.edu
Vreede
Andrew P
AP
Kim
Susie
S
Golden
Jeffrey
J
Feldman
Eva L
EL
D000818:Animals; D029742:Caenorhabditis elegans Proteins; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules; D002454:Cell Differentiation; D002460:Cell Line; D048430:Cell Shape; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D016023:Integrins; D051379:Mice; D032342:Muscle Cells / Q000166:cytology*; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal; D009124:Muscle Proteins / Q000235:genetics / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
D029742:Caenorhabditis elegans Proteins; D015815:Cell Adhesion Molecules; D003598:Cytoskeletal Proteins; D016023:Integrins; D009124:Muscle Proteins; D017346:Protein Serine-Threonine Kinases; D000099200:Scaffold Protein ILK; C411729:UNC-112 protein, C elegans; C527802:kindlin-2 protein, mouse