MTM1-mediated production of phosphatidylinositol 5-phosphate fuels the formation of podosome-like protrusions regulating myoblast fusion
Myoblast fusion into multinuclear myotubes is a critical cellular process for the formation of skeletal muscle fibers. However, the mechanisms orchestrating cell fusion remain incompletely understood. In this study, using a cellular model of X-linked centronuclear myopathy, in which the phosphoinositide phosphatase MTM1 has been knockout, we unravel an unexpected pathway connecting MTM1 to cell-cell fusion. We demonstrate that MTM1 is the main enzyme in this cellular system responsible for synthesizing PI5P. Subsequently, PI5P is rapidly metabolized by the PI5P 4-kinase α into PI(4,5)P2 which accumulates at the plasma membrane thereby facilitating the formation of podosome-like protrusions, playing a crucial role in the spatiotemporal regulation of myoblast fusion.
