意大利都灵大学Emilio Hirsch、ederico Gulluni研究组在研究中取得进展。他们发现PI(3,4)P2 介导的细胞因子脱落防止早期衰老和白内障发生。该项研究成果发表在2021年12月10日出版的《科学》上。
研究人员发现了一种晶状体特异性细胞因子过程，它需要PI3K-C2α（磷脂酰肌醇-4-磷酸3-激酶催化2α亚型）、其脂质产物PI(3,4)P2（磷脂酰肌醇 3,4-二磷酸）和PI (3,4)P2结合ESCRT-II亚基VPS36（液泡蛋白分选相关蛋白36）。每一种成分的缺失都会导致胞质分裂受损，从而引发鱼、小鼠和人类晶状体的过早衰老。因此，该进化保守途径是细胞分裂过程中细胞类型特异性调控的基础，它有助于通过阻碍衰老来预防早发性白内障。
据了解，细胞膜脱落动力学是由空间和时间调控的过程，需要ESCRT（运输所需的内体分选复合物）依赖的控制中间体膜重塑，中间体是一种定义切割位点的亚细胞细胞器。ESCRT功能的改变可导致白内障，但其潜在机制及其与胞质分裂的关系尚不清楚。
附：英文原文
Title: PI(3,4)P2-mediated cytokinetic abscission prevents early senescence and cataract formation
Author: Federico Gulluni, Lorenzo Prever, Huayi Li, Petra Krafcikova, Ilaria Corrado, Wen-Ting Lo, Jean Piero Margaria, Anlu Chen, Maria Chiara De Santis, Sophie J. Cnudde, Joseph Fogerty, Alex Yuan, Alberto Massarotti, Nasrin Torabi Sarijalo, Oscar Vadas, Roger L. Williams, Marcus Thelen, David R. Powell, Markus Schueler, Michael S. Wiesener, Tamas Balla, Hagit N. Baris, Dov Tiosano, Brian M. McDermottJr., Brian D. Perkins, Alessandra Ghigo, Miriam Martini, Volker Haucke, Evzen Boura, Giorgio Roberto Merlo, David A. Buchner, Emilio Hirsch
Issue&Volume: 2021-12-10
Abstract: Cytokinetic membrane abscission is a spatially and temporally regulated process that requires ESCRT (endosomal sorting complexes required for transport)–dependent control of membrane remodeling at the midbody, a subcellular organelle that defines the cleavage site. Alteration of ESCRT function can lead to cataract, but the underlying mechanism and its relation to cytokinesis are unclear. We found a lens-specific cytokinetic process that required PI3K-C2α (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2α), its lipid product PI(3,4)P2 (phosphatidylinositol 3,4-bisphosphate), and the PI(3,4)P2–binding ESCRT-II subunit VPS36 (vacuolar protein-sorting-associated protein 36). Loss of each of these components led to impaired cytokinesis, triggering premature senescence in the lens of fish, mice, and humans. Thus, an evolutionarily conserved pathway underlies the cell type–specific control of cytokinesis that helps to prevent early onset cataract by protecting from senescence.
DOI: abk0410
Source: https://www.science.org/doi/10.1126/science.abk0410