Martin Claire, Gunning Peter
Oncology Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Australia.
Adv Exp Med Biol. 2008;644:187-200. doi: 10.1007/978-0-387-85766-4_15.
Cytoskeletal tropomyosin (Tm) isoforms show extensive intracellular sorting, resulting in spatially distinct actin-filament populations. Sorting of Tm isoforms has been observed in a number of cell types, including fibroblasts, epithelial cells, osteoclasts, neurons and muscle cells. Different Tm isoforms have differential impact on the activity of a number of actin-binding proteins and can therefore differentially regulate actin filament function. Functionally distinct sub-populations of actin filaments can therefore be defined on the basis of the Tm isoforms associated with the filaments. The mechanisms that underlie Tm sorting are not yet well understood, but it is clear that Tm sorting is a very fluid and dynamic process, with changes in sorting occurring throughout development and cell differentiation. For this reason, it is unlikely that Tm localization is determined by an intrinsic sorting signal that directs particular isoforms to a single geographical location. Rather, a molecular sink model where isoforms accumulate in actin-based structures where they have the highest affinity, is most consistent with current data. This model would predict Tm sorting to be influenced by changes to actin filament dynamics and organization and collaboration with other actin-binding proteins.
细胞骨架原肌球蛋白（Tm）异构体表现出广泛的细胞内分选现象，导致肌动蛋白丝群体在空间上呈现出不同分布。在包括成纤维细胞、上皮细胞、破骨细胞、神经元和肌肉细胞在内的多种细胞类型中都观察到了Tm异构体的分选现象。不同的Tm异构体对多种肌动蛋白结合蛋白的活性有不同影响，因此能够以不同方式调节肌动蛋白丝的功能。因此，基于与肌动蛋白丝相关的Tm异构体，可以定义功能不同的肌动蛋白丝亚群。Tm分选背后的机制尚未完全清楚，但很明显，Tm分选是一个非常灵活且动态的过程，在整个发育和细胞分化过程中，分选情况都会发生变化。因此，Tm的定位不太可能由一个内在的分选信号决定，该信号将特定异构体导向单一的地理位置。相反，一种分子汇模型，即异构体在与其具有最高亲和力的基于肌动蛋白的结构中积累，与当前数据最为一致。该模型预测Tm分选会受到肌动蛋白丝动力学和组织变化以及与其他肌动蛋白结合蛋白协作的影响。
