MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome- like protrusions regulating myoblast fusion

• 成果类型: Article
• 署名作者: Mansat, Melanie; Kpotor, Afi Oportune; Chicanne, Gaetan; Picot, Melanie; Mazars, Anne; Flores- Flores, Remy; Payrastre, Bernard; Hnia, Karim; Viaud, Julien
• 署名单位: Institut National de la Sante et de la Recherche Medicale (Inserm); Universite de Toulouse; Universite Toulouse III - Paul Sabatier; CHU de Toulouse
• 刊物名称: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
• ISSN/ISSBN: 0027-11157
• DOI: 10.1073/pnas.2217971121
• 发表日期: 2024-06-04
• 关键词: myotubular myopathy; phosphoinositides; pi(4; 5)p-2; cells; MODEL

摘要

Myogenesis is a multistep process that requires a spatiotemporal regulation of cell events resulting finally in myoblast fusion into multinucleated myotubes. Most major insights into the mechanisms underlying fusion seem to be conserved from insects to mammals and include the formation of podosome - like protrusions (PLPs) that exert a driving force toward the founder cell. However, the machinery that governs this process remains poorly understood. In this study, we demonstrate that MTM1 is the main enzyme responsible for the production of phosphatidylinositol 5 - phosphate, which in turn fuels PI5P 4 - kinase alpha to produce a minor and functional pool of phosphatidylinositol 4,5 - bisphosphate that concentrates in PLPs containing the scaffolding protein Tks5, Dynamin - 2, and the fusogenic protein Myomaker. Collectively, our data reveal a functional crosstalk between a PI - phosphatase and a PI - kinase in the regulation of PLP formation.