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PMID: 18268005 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Molecular and cellular biology ·Vol. 28 ·No. 8 ·2008-04-00 ·Pages 2637-47

Stiber JA, Zhang ZS, Burch J, Eu JP, Zhang S, Truskey GA, Seth M, Yamaguchi N, Meissner G, Shah R, Worley PF, Williams RS, Rosenberg PB

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.

MeSH Terms
Animals Calcium Signaling Carrier Proteins/genetics,metabolism Cells, Cultured Disease Models, Animal Gene Deletion Gene Expression Regulation Homer Scaffolding Proteins Mice Mice, Knockout Muscle Contraction Muscular Dystrophies/genetics,pathology,physiopathology Protein Binding TRPC Cation Channels/genetics,metabolism
Chemicals
Carrier Proteins Homer Scaffolding Proteins TRPC Cation Channels
Authors & Affiliations
13 authors, click to expand affiliations / ORCID
Stiber Jonathan A
Department of Medicine, Duke University Medical Center, 4321 Medical Park Drive, Suite 200, Durham, NC 27704, USA.
Zhang Zhu-Shan
Burch Jarrett
Eu Jerry P
Zhang Sarah
Truskey George A
Seth Malini
Yamaguchi Naohiro
Meissner Gerhard
Shah Ripal
Worley Paul F
Williams R Sanders
Rosenberg Paul B
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Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
1098-5549
DOI
10.1128/MCB.01601-07
Published
2008-04-00
Epub
2008-00-11
Pages
2637-47
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC2293116
Subset
IM
Grants
NHLBI NIH HHS · K08 HL071841 · United States
NHLBI NIH HHS · K08 HL077520 · United States
NHLBI NIH HHS · R01 HL093470 · United States
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1128/MCB.01601-07 PMC Full Text View journal details
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