Mice lacking Homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity.

TitleMice lacking Homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity.
Publication TypeJournal Article
Year of Publication2008
AuthorsStiber, JA, Zhang, Z-S, Burch, J, Eu, JP, Zhang, S, Truskey, GA, Seth, M, Yamaguchi, N, Meissner, G, Shah, R, Worley, PF, Williams, RS, and Rosenberg, PB
JournalMolecular and Cellular Biology
Volume28
Issue8
Start Page2637
Pagination2637 - 2647
Date Published04/2008
Abstract

Transient receptor potential (TRP) 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 1 exhibited a myopathy characterized by decreased muscle fiber cross-sectional area and decreased skeletal muscle force generation. Homer 1 knockout myotubes displayed increased basal current density and spontaneous cation influx. This spontaneous cation influx in Homer 1 knockout myotubes was blocked by reexpression of Homer 1b, but not Homer 1a, and by gene silencing of TRPC1. Moreover, diminished Homer 1 expression in mouse models of Duchenne's muscular dystrophy suggests that loss of Homer 1 scaffolding of TRP channels may contribute to the increased stretch-activated channel activity observed in mdx myofibers. These findings provide direct evidence that Homer 1 functions as an important scaffold for TRP channels and regulates mechanotransduction in skeletal muscle.

DOI10.1128/MCB.01601-07
Short TitleMolecular and Cellular Biology