Mol Cell Biol. 2008 Apr;28(8):2637-47. doi: 10.1128/MCB.01601-07. Epub 2008 Feb 11.
Mice lacking Homer 1 exhibit a skeletal myopathy characterized by abnormal transient receptor potential channel activity.
Stiber, J. A., Zhang, Z. S., Burch, J., Eu, J. P., Zhang, S., Truskey, G. A., Seth, M., Yamaguchi, N., Meissner, G., Shah, R., Worley, P. F., Williams, R. S., Rosenberg, P. B.,
["Department of Medicine, Duke University Medical Center, 4321 Medical Park Drive, Suite 200, Durham, NC 27704, USA."]
["Department of Medicine, Duke University Medical Center, 4321 Medical Park Drive, Suite 200, Durham, NC 27704, USA."]
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.
PMID: 18268005
 Screening
Validation: In vitro validation
Validation: In vivo validation
Characterization
Functional consequence
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Validation: In vivo validation
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| Assay with endogenous proteins | Assay with overexpressed proteins | Reference | ||||||||
| Cell or tissue | Cell or tissue | TRP channel construct | Interactor construct | |||||||
| TRP channel | Interactor | Method | Species | Region | Species | Region | ||||
| TRPC1 |
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Homer | Co-immunofluorescence staining | Mouse skeletal muscle | 18268005 | |||||
| TRPC1 |
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Homer | Co-immunoprecipitation | Mouse skeletal muscle | 18268005 | |||||
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click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)
:
click the arrow icon to show interactions only between the corresponding TRP channel and the interactor)