PDF(Pubmed)
Abstract：
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 α 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.
摘要：
成肌是一个多步骤的过程，需要对细胞事件进行时空调节，最终导致成肌细胞融合到多核肌管中。对融合机制的最主要见解似乎从昆虫到哺乳动物都是保守的，包括形成足体样突起（PLPs），对创始人细胞产生驱动力。然而,控制这一过程的机制仍然知之甚少。在这项研究中,我们证明MTM1是负责生产磷脂酰肌醇5-磷酸的主要酶，反过来又为PI5P4-激酶α提供燃料，以产生少量的功能性磷脂酰肌醇4,5-双磷酸酯池，该池浓缩在含有支架蛋白Tks5，Dynamin-2和融合蛋白Myomaker的PLP中。总的来说，我们的数据揭示了在调节PLP形成过程中PI-磷酸酶和PI-激酶之间的功能性串扰。
