Isoform sorting of tropomyosins

Abstract

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.