Manor Uri, Schiavon Cara, Wang Yuning, Feng Jasmine, Garrett Stephanie, Sung Tsung-Chang, Dayn Yelena, Shadel Gerald, Quintero-Carmona Omar, Wang Chunxin, Youle Richard J
Res Sq. 2024 Aug 16:rs.3.rs-4720604. doi: 10.21203/rs.3.rs-4720604/v1.
Proper regulation of organelle dynamics and inter-organelle contacts is critical for cellular health and function. Both the endoplasmic reticulum (ER) and actin cytoskeleton are known to regulate organelle dynamics, but how, when, and where these two subcellular components are coordinated to control organelle dynamics remains unclear. Here, we show that ER-associated actin consistently marks mitochondrial, endosomal, and lysosomal fission sites. We also show that actin polymerization by the ER-anchored isoform of the formin protein INF2 is a key regulator of the morphology and mobility of these organelles. Together, our findings establish a mechanism by which INF2-mediated polymerization of ER-associated actin at ER-organelle contacts regulates organelle dynamics.
细胞器动态变化和细胞器间接触的适当调节对于细胞健康和功能至关重要。已知内质网(ER)和肌动蛋白细胞骨架都能调节细胞器动态变化,但这两个亚细胞成分如何、何时以及在何处协同控制细胞器动态变化仍不清楚。在这里,我们表明内质网相关的肌动蛋白始终标记线粒体、内体和溶酶体的分裂位点。我们还表明,由formin蛋白INF2的内质网锚定异构体介导的肌动蛋白聚合是这些细胞器形态和移动性的关键调节因子。总之,我们的研究结果建立了一种机制,通过该机制,内质网与细胞器接触处的INF2介导的内质网相关肌动蛋白聚合调节细胞器动态变化。