| Autor: |
Zhang, S., Burch, J., Williams, R. S., Worley, P. F., Zhang, Z.-S., Yamaguchi, N., Eu, J. P., Rosenberg, P. B., Truskey, G. A., Meissner, G., Seth, M., Stiber, J. A., Shah, R. |
| Jazyk: |
angličtina |
| Rok vydání: |
2008 |
| DOI: |
10.17615/zyge-0571 |
| Popis: |
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. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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