Skeletal muscle LIM protein 1 regulates integrin-mediated myoblast adhesion, spreading, and migration.
The skeletal muscle LIM protein 1 (SLIM1) is highly expressed in skeletal and cardiac muscle, and its expression is downregulated significantly in dilated human cardiomyopathy. However, the function of SLIM1 is unknown. In this study, we investigated the intracellular localization of SLIM1. Endogenous and recombinant SLIM1 localized to the nucleus, stress fibers, and focal adhesions in skeletal myoblasts plated on fibronectin, collagen, or laminin. However, after inhibition of integrin signaling either by plating on poly-l-lysine or by soluble RGD peptide, SLIM1 localized diffusely in the cytosol, with decreased nuclear expression. Disruption of the actin cytoskeleton by cytochalasin D did not inhibit nuclear localization of SLIM1 in integrin-activated cells. Green fluorescent protein-tagged SLIM1 shuttled in the nucleus of untransfected NIH 3T3 cells, in a heterokaryon fusion assay. Overexpression of SLIM1 in Sol8 myoblasts inhibited cell adhesion and promoted cell spreading and migration. These studies show SLIM1 localizes in an integrin-dependent manner to the nucleus and focal adhesions where it functions downstream of integrin activation to promote cell spreading and migration.
Robinson
Paul A
PA
Department of Biochemistry and Molecular Biology, Monash University, Clayton, Victoria, Australia 3168.
Brown
Susan
S
McGrath
Meagan J
MJ
Coghill
Imogen D
ID
Gurung
Rajendra
R
Mitchell
Christina A
CA
D016475:3T3 Cells; D008841:Actin Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D021581:Active Transport, Cell Nucleus / Q000187:drug effects / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology*; D002451:Cell Compartmentation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D002467:Cell Nucleus / Q000235:genetics / Q000378:metabolism; D015638:Cytochalasin D / Q000494:pharmacology; D022001:Focal Adhesions / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D016023:Integrins / Q000378:metabolism*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000196:embryology* / Q000378:metabolism*; D032448:Myoblasts, Skeletal / Q000166:cytology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D022502:Stress Fibers / Q000235:genetics / Q000378:metabolism
D018398:Homeodomain Proteins; D016023:Integrins; D015638:Cytochalasin D