Tropomyosin isoform 3 promotes the formation of filopodia by regulating the recruitment of actin-binding proteins to actin filaments |
| |
Authors: | Creed Sarah J Desouza Melissa Bamburg James R Gunning Peter Stehn Justine |
| |
Affiliation: | aOncology Research Unit, The Children's Hospital at Westmead, Westmead NSW, Australia;bDepartment of Biochemistry and Molecular Biology, Colorado State University, Fort Collins CO, USA;cOncology Research Unit, Department of Pharmacology, School of Medical Sciences, Rm 502, Wallace Wurth (C27), University of NSW, Sydney NSW, 2052, Australia;dDiscipline of Paediatrics and Child Health, University of Sydney, Sydney NSW, Australia |
| |
Abstract: | Tropomyosins are believed to function in part by stabilizing actin filaments. However, accumulating evidence suggests that fundamental differences in function exist between tropomyosin isoforms, which contributes to the formation of functionally distinct filament populations. We investigated the functions of the high-molecular-weight isoform Tm3 and examined the molecular properties of Tm3-containing actin filament populations. Overexpression of the Tm3 isoform specifically induced the formation of filopodia and changes in actin solubility. We observed alterations in actin-binding protein recruitment to filaments, co-incident with changes in expression levels, which can account for this functional outcome. Tm3-associated filaments recruit active actin depolymerizing factor and are bundled into filopodia by fascin, which is both up-regulated and preferentially associated with Tm3-containing filaments in the Tm3 overexpressing cells. This study provides further insight into the isoform-specific roles of different tropomyosin isoforms. We conclude that variation in the tropomyosin isoform composition of microfilaments provides a mechanism to generate functionally distinct filament populations. |
| |
Keywords: | Abbreviations: ABP(s), actin-binding protein(s) ADF, actin depolymerizing factor Arp, actin-related protein HMW, high molecular weight LimK, Lim kinase LMW, low molecular weight PBS, phosphate-buffered saline s.d., standard deviation Tm(s), tropomyosin(s) |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|