Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/53630
Title: P130CAS-DEPENDENT ACTIN REMODELING REGULATES MYOGENIC DIFFERENTIATION
Authors: TAN WEE WEE
Keywords: p130Cas, C2C12, actin remodeling, myogenesis, differentiation
Issue Date: 24-Jul-2013
Source: TAN WEE WEE (2013-07-24). P130CAS-DEPENDENT ACTIN REMODELING REGULATES MYOGENIC DIFFERENTIATION. ScholarBank@NUS Repository.
Abstract: Myogenesis comprises a series of tightly regulated steps mediated by myogenic regulatory factors. Disruptions in the myogenic signaling pathways block myogenic progression, leading to an impaired muscular development. In this study, the importance of p130Cas in skeletal myogenic differentiation was addressed using murine myoblastic C2C12 cells to investigate the regulatory mechanism involved in the facilitation of myotube formation. Silencing of p130Cas expression by RNA interference impaired F-actin formation and nuclear localization of the SRF co-activator MAL following the induction of myogenic differentiation. Consequently, formation of multinucleated myotubes was abolished. Re-introduction of wild-type p130Cas, but not its phosphorylation-defective mutant, into p130Cas-knockdown myoblasts restored F-actin assembly, MAL nuclear localization and myotube formation. Depletion of the adhesion molecule integrin ß3, a key regulator of myogenic differentiation as well as actin cytoskeletal organization, attenuated p130Cas phosphorylation and MAL nuclear localization during C2C12 differentiation. Moreover, knockdown of p130Cas led to the activation of the F-actin severing protein cofilin. The introduction of a dominant-negative mutant of cofilin into p130Cas-knockdown myoblasts restored muscle-specific gene expression and myotube formation. Together, these results demonstrated the essential role of p130Cas for skeletal myogenic progression in C2C12 myoblasts and that the phosphorylation of p130Cas, mediated by integrin ß3, facilitated cofilin inactivation to promote myogenic differentiation through modulation of actin cytoskeleton remodeling and enhancing MAL/SRF transcriptional activity.
URI: http://scholarbank.nus.edu.sg/handle/10635/53630
Appears in Collections:Ph.D Theses (Open)

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