Publications

Publication Search

Search for publications by

Grb10 deletion enhances muscle cell proliferation, differentiation and GLUT4 plasma membrane translocation

Abstract

Grb10 is an intracellular adaptor protein which binds directly to several growth factor receptors, including those for insulin and insulin-like growth factor receptor-1 (IGF-1), and negatively regulates their actions. Grb10-ablated (Grb10(-/-) ) mice exhibit improved whole body glucose homeostasis and an increase in muscle mass associated specifically with an increase in myofiber number. This suggests that Grb10 may act as a negative regulator of myogenesis. In this study, we investigated in vitro, the molecular mechanisms underlying the increase in muscle mass and the improved glucose metabolism. Primary muscle cells isolated from Grb10(-/-) mice exhibited increased rates of proliferation and differentiation compared to primary cells isolated from wild-type mice. The improved proliferation capacity was associated with an enhanced phosphorylation of Akt and ERK in the basal state and changes in the expression of key cell cycle progression markers involved in regulating transition of cells from the G1 to S phase (e.g., retinoblastoma (Rb) and p21). The absence of Grb10 also promoted a faster transition to a myogenin positive, differentiated state. Glucose uptake was higher in Grb10(-/-) primary myotubes in the basal state and was associated with enhanced insulin signaling and an increase in GLUT4 translocation to the plasma membrane. These data demonstrate an important role for Grb10 as a link between muscle growth and metabolism with therapeutic implications for diseases, such as muscle wasting and type 2 diabetes. J. Cell. Physiol. 229: 1753-1764, 2014. (c) 2014 Wiley Periodicals, Inc.

Type Journal
ISBN 1097-4652 (Electronic) 0021-9541 (Linking)
Authors Mokbel, N.; Hoffman, N. J.; Girgis, C. M.; Small, L.; Turner, N.; Daly, R. J.; Cooney, G. J.; Holt, L. J.;
Garvan Authors Christian Girgis , Prof Gregory Cooney , Lewin Small , Dr Lowenna Holt , Dr Nigel Turner
Publisher Name J CELL PHYSIOL
Published Date 2014-01-01 00:00:00
Published Volume 229
Published Issue 11
Published Pages 1753-64
URL http://www.ncbi.nlm.nih.gov/pubmed/24664951
Status Published In-print
OpenAccess Link https://publications.gimr.garvan.org.au/download.php?12398_12930/14_Mokbel_JCP_.pdf