Tks5 and Dynamin-2 Enhance Actin Bundle Rigidity in Invadosomes to Promote Myoblast Fusion

Overview

Journal J Cell Biol

Specialty Cell Biology

Date 2019 Mar 22

PMID 30894403

Citations 21

Authors

Mei-Chun Chuang

Shan-Shan Lin

Ryosuke L Ohniwa

Gang-Hui Lee

You-An Su

Yu-Chen Chang

Ming-Jer Tang

Ya-Wen Liu

Affiliations

Soon will be listed here.

Abstract

Skeletal muscle development requires the cell-cell fusion of differentiated myoblasts to form muscle fibers. The actin cytoskeleton is known to be the main driving force for myoblast fusion; however, how actin is organized to direct intercellular fusion remains unclear. Here we show that an actin- and dynamin-2-enriched protrusive structure, the invadosome, is required for the fusion process of myogenesis. Upon differentiation, myoblasts acquire the ability to form invadosomes through isoform switching of a critical invadosome scaffold protein, Tks5. Tks5 directly interacts with and recruits dynamin-2 to the invadosome and regulates its assembly around actin filaments to strengthen the stiffness of dynamin-actin bundles and invadosomes. These findings provide a mechanistic framework for the acquisition of myogenic fusion machinery during myogenesis and reveal a novel structural function for Tks5 and dynamin-2 in organizing actin filaments in the invadosome to drive membrane fusion.

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