Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

Jonathan A. Stiber; Zhu-Shan Zhang; Jarrett Burch; Jerry P. Eu; Sarah Zhang; George A. Truskey; Malini Seth; Naohiro Yamaguchi; Gerhard Meissner; Ripal Shah; Paul F. Worley; R. Sanders Williams; Paul B. Rosenberg

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Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

机译：缺少荷马1的小鼠表现出以异常瞬时受体潜在通道活性异常为特征的骨骼肌病

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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.

机译：瞬时受体电位（TRP）通道是非选择性阳离子通道，其中一些在横纹肌中表达。因为脚手架蛋白质荷马蛋白1已牵涉到TRP通道调节，我们假设荷马蛋白在骨骼肌功能中起重要作用。缺乏荷马1的小鼠表现出一种肌病，其特征是肌纤维横截面积减少和骨骼肌力生成减少。荷马1基因敲除肌管显示增加的基础电流密度和自发的阳离子涌入。 Homer 1基因敲除肌管中的这种自发性阳离子流入被Homer 1b的表达而不是Homer 1a的表达以及TRPC1的基因沉默所阻止。此外，在杜兴氏肌营养不良的小鼠模型中Homer 1表达的减少表明TRP通道的Homer 1支架的丧失可能有助于在 mdx 肌纤维中观察到的拉伸激活通道活性的增加。这些发现提供了直接的证据，证明荷马1充当TRP通道的重要支架并调节骨骼肌的机械传导。 展开▼

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《Molecular and Cellular Biology》 |2008年第8期|共11页

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Jonathan A. Stiber; Zhu-Shan Zhang; Jarrett Burch; Jerry P. Eu; Sarah Zhang; George A. Truskey; Malini Seth; Naohiro Yamaguchi; Gerhard Meissner; Ripal Shah; Paul F. Worley; R. Sanders Williams; Paul B. Rosenberg;
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中图分类细胞生物学;

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1. Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1 [J] . Maftei Daniela, Vellani Vittorio, Artico Marco, Neuroscience: An International Journal under the Editorial Direction of IBRO . 2020,第1期

机译：小鼠疼痛感觉异常疼痛感染缺血受体PKR2：PKR2与瞬态受体电位TRPV1和TRPA1的相互作用

2. Reduced oral ethanol avoidance in mice lacking transient receptor potential channel vanilloid receptor 1. [J] . Ellingson JM, Silbaugh BC, Brasser SM Behavior Genetics: An International Journal Devoted to Research in the Inheritance of Behavior in Animals and Man . 2009,第1期

机译：缺乏瞬态受体电位通道香草素受体1的小鼠口服乙醇避免减少。

3. Reduced Oral Ethanol Avoidance in Mice Lacking Transient Receptor Potential Channel Vanilloid Receptor 1 [J] . Jarrod M. Ellingson, Bryant C. Silbaugh, Susan M. Brasser Behavior Genetics . 2009,第1期

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4. The functional efficiency of lipogenic and cholesterogenic gene expression in normal miceand in mice lacking the peroxisomal proliferator-activated receptor-alpha (PPAR-α) [C] . Geoffrey F. Gibbons, Dilip Patel, David Wiggins, International Symposium on Regulation of Enzyme Activity and Synthesis in Normal and Neoplastic Tissues . 2003

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6. Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity [O] . Jonathan A. Stiber, Zhu-Shan Zhang, Jarrett Burch, 2008

机译：缺乏荷马1的小鼠表现出以异常瞬时受体潜在通道活性为特征的骨骼肌病

7. Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity▿ † [O] . Stiber, Jonathan A., Zhang, Zhu-Shan, Burch, Jarrett, 2008

机译：缺乏荷马1的小鼠表现出以异常瞬时受体潜在通道活性异常为特征的骨骼肌病

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Mice Lacking Homer 1 Exhibit a Skeletal Myopathy Characterized by Abnormal Transient Receptor Potential Channel Activity

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