Vlahovich Nicole, Kee Anthony J, Van der Poel Chris, Kettle Emma, Hernandez-Deviez Delia, Lucas Christine, Lynch Gordon S, Parton Robert G, Gunning Peter W, Hardeman Edna C
Muscle Development Unit, Children's Medical Research Institute, Westmead, NSW, Australia.
Mol Biol Cell. 2009 Jan;20(1):400-9. doi: 10.1091/mbc.e08-06-0616. Epub 2008 Nov 12.
The functional diversity of the actin microfilaments relies in part on the actin binding protein tropomyosin (Tm). The muscle-specific Tms regulate actin-myosin interactions and hence contraction. However, there is less known about the roles of the numerous cytoskeletal isoforms. We have shown previously that a cytoskeletal Tm, Tm5NM1, defines a Z-line adjacent cytoskeleton in skeletal muscle. Recently, we identified a second cytoskeletal Tm in this region, Tm4. Here we show that Tm4 and Tm5NM1 define separate actin filaments; the former associated with the terminal sarcoplasmic reticulum (SR) and other tubulovesicular structures. In skeletal muscles of Tm5NM1 knockout (KO) mice, Tm4 localization was unchanged, demonstrating the specificity of the membrane association. Tm5NM1 KO muscles exhibit potentiation of T-system depolarization and decreased force rundown with repeated T-tubule depolarizations consistent with altered T-tubule function. These results indicate that a Tm5NM1-defined actin cytoskeleton is required for the normal excitation-contraction coupling in skeletal muscle.
肌动蛋白微丝的功能多样性部分依赖于肌动蛋白结合蛋白原肌球蛋白（Tm）。肌肉特异性的Tm调节肌动蛋白与肌球蛋白的相互作用，从而调节收缩。然而，对于众多细胞骨架异构体的作用了解较少。我们之前已经表明，一种细胞骨架Tm，即Tm5NM1，在骨骼肌中定义了一种与Z线相邻的细胞骨架。最近，我们在该区域鉴定出了第二种细胞骨架Tm，即Tm4。在此我们表明，Tm4和Tm5NM1定义了不同的肌动蛋白丝；前者与终末肌浆网（SR）及其他小管泡状结构相关。在Tm5NM1基因敲除（KO）小鼠的骨骼肌中，Tm4的定位未发生变化，这证明了膜结合的特异性。Tm5NM1基因敲除的肌肉表现出T系统去极化增强，并且在重复的T小管去极化时力衰减减少，这与T小管功能改变一致。这些结果表明，Tm5NM1定义的肌动蛋白细胞骨架是骨骼肌正常兴奋 - 收缩偶联所必需的。
