|Title||Mice lacking homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity|
|Publication Type||Journal Article|
|Year of Publication||2008|
|Authors||JA Stiber, ZS Zhang, J Burch, JP Eu, S Zhang, GA Truskey, M Seth, N Yamaguchi, G Meissner, R Shah, PF Worley, RS Williams, and PB Rosenberg|
|Journal||Molecular and Cellular Biology|
|Pagination||2637 - 2647|
Transient receptor potential (TRIP) channels are nonselective cation channels, several of which are expressed in striated muscle. Because the scaffolding protein Homer 1 has been implicated in TRP channel regulation, we hypothesized that Homer proteins play a significant role in skeletal muscle function. Mice lacking Homer I exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer I knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer I knockout myotubes was blocked by reexpression of Homer 1b, but not Homer la, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer I scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdr myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.
|Short Title||Molecular and Cellular Biology|