Tropomyosin - master regulator of actin filament function in the cytoskeleton
Tropomyosin - master regulator of actin filament function in the cytoskeleton
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DOI：
10.1242/jcs.172502
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发表时间：
2015-08-15
影响因子：
4
通讯作者：
Mulvihill, Daniel P.
中科院分区：
文献类型：
--
作者：
Gunning, Peter W.;Hardeman, Edna C.;Mulvihill, Daniel P.
原肌球蛋白（Tpm）异构体是真菌和后生动物中单个肌动蛋白丝功能的主要调节因子。Tpms是一种螺旋状平行二聚体，沿着肌动蛋白丝的长度形成首尾相连的聚合物。酵母只有两个Tpm亚型，而哺乳动物有40多个。每个细胞骨架肌动蛋白丝含有Tpm同二聚体的均聚物，从而形成沿其长度均匀的Tpm组成的丝。这种“主监管者”作用的证据基于四组核心观察。首先，在空间和功能上不同的肌动蛋白丝含有不同的Tpm异构体，最近的数据表明，肌动蛋白丝成核者的formin家族成员可以指定哪个Tpm异构体被添加到生长的肌动蛋白丝中。其次，Tpms在形态发生、细胞增殖、囊泡运输、生物力学、葡萄糖代谢和器官大小等方面以同种异构体特异性的方式调节整个生物体的生理。第三，Tpms通过以同种异构体特异性的方式调节肌动蛋白丝与肌球蛋白马达和肌动蛋白结合蛋白的相互作用来实现这些功能输出。最后，复杂结构的组装，如应力纤维和足小体，涉及由其Tpm组成的多种类型的肌动蛋白丝的协作。这允许细胞通过简单地指定其Tpm异构体组成来指定肌动蛋白丝在时间和空间上的功能。
Tropomyosin (Tpm) isoforms are the master regulators of the functions of individual actin filaments in fungi and metazoans. Tpms are coiled-coil parallel dimers that form a head-to-tail polymer along the length of actin filaments. Yeast only has two Tpm isoforms, whereas mammals have over 40. Each cytoskeletal actin filament contains a homopolymer of Tpm homodimers, resulting in a filament of uniform Tpm composition along its length. Evidence for this 'master regulator' role is based on four core sets of observation. First, spatially and functionally distinct actin filaments contain different Tpm isoforms, and recent data suggest that members of the formin family of actin filament nucleators can specify which Tpm isoform is added to the growing actin filament. Second, Tpms regulate whole-organism physiology in terms of morphogenesis, cell proliferation, vesicle trafficking, biomechanics, glucose metabolism and organ size in an isoform-specific manner. Third, Tpms achieve these functional outputs by regulating the interaction of actin filaments with myosin motors and actin-binding proteins in an isoform-specific manner. Last, the assembly of complex structures, such as stress fibers and podosomes involves the collaboration of multiple types of actin filament specified by their Tpm composition. This allows the cell to specify actin filament function in time and space by simply specifying their Tpm isoform composition.