Differential roles of HIC-5 isoforms in the regulation of cell death and myotube formation during myogenesis.
Hic-5 is a LIM-Only member of the paxillin superfamily of focal adhesion proteins. It has been shown to regulate a range of biological processes including: senescence, tumorigenesis, steroid hormone action, integrin signaling, differentiation, and apoptosis. To better understand the roles of Hic-5 during development, we initiated a detailed analysis of Hic-5 expression and function in C(2)C(12) myoblasts, a well-established model for myogenesis. We have found that: (1) myoblasts express at least 6 distinct Hic-5 isoforms; (2) the two predominant isoforms, Hic-5alpha and Hic-5beta, are differentially expressed during myogenesis; (3) any experimentally induced change in Hic-5 expression results in a substantial increase in apoptosis during differentiation; (4) ectopic expression of Hic-5alpha is permissive to differentiation while expression of either Hic-5beta or antisense Hic-5 blocks myoblast fusion but not chemodifferentiation; (5) Hic-5 localizes to focal adhesions in C(2)C(12) myoblasts and perturbation of Hic-5 leads to defects in cell spreading; (6) alterations in Hic-5 expression interfere with the normal dynamics of laminin expression; and (7) ectopic laminin, but not fibronectin, can rescue the Hic-5-induced blockade of myoblast survival and differentiation. Our data demonstrate differential roles for individual Hic-5 isoforms during myogenesis and support the hypothesis that Hic-5 mediates these effects via integrin signaling.
Gao
Zheng-Liang
ZL
Molecular and Cellular Biology Program, University of Massachusetts, Amherst, MA 01003, USA.
Deblis
Ryan
R
Glenn
Honor
H
Schwartz
Lawrence M
LM
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D022001:Focal Adhesions; D016023:Integrins; D060588:LIM Domain Proteins; D051379:Mice; D024510:Muscle Development; D018485:Muscle Fibers, Skeletal; D032446:Myoblasts; D020033:Protein Isoforms / Q000502:physiology; D015398:Signal Transduction
D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; D016023:Integrins; D060588:LIM Domain Proteins; D020033:Protein Isoforms; C090090:Tgfb1i1 protein, mouse