Department of Biological Sciences, University of Denver, Denver, CO 80208, USA.
Development. 2023 Aug 15;150(16). doi: 10.1242/dev.201547. Epub 2023 Aug 17.
Ingression of the plasma membrane is an essential part of the cell topology-distorting repertoire and a key element in animal cell cytokinesis. Many embryos have rapid cleavage stages in which they are furrowing powerhouses, quickly forming and disassembling cleavage furrows on timescales of just minutes. Previous work has shown that cytoskeletal proteins and membrane trafficking coordinate to drive furrow ingression, but where these membrane stores are derived from and how they are directed to furrowing processes has been less clear. Here, we identify an extensive Rab35/Rab4>Rab39/Klp98A>trans-Golgi network (TGN) endocytic recycling pathway necessary for fast furrow ingression in the Drosophila embryo. Rab39 is present in vesiculotubular compartments at the TGN where it receives endocytically derived cargo through a Rab35/Rab4-dependent pathway. A Kinesin-3 family member, Klp98A, drives the movements and tubulation activities of Rab39, and disruption of this Rab39-Klp98A-Rab35 pathway causes deep furrow ingression defects and genomic instability. These data suggest that an endocytic recycling pathway rapidly remobilizes membrane cargo from the cell surface and directs it to the trans-Golgi network to permit the initiation of new cycles of cleavage furrow formation.
质膜内陷是细胞拓扑结构扭曲的重要组成部分，也是动物细胞胞质分裂的关键元素。许多胚胎具有快速分裂阶段，在这些阶段中，它们是褶皱的动力源，能够在几分钟的时间内快速形成和解离分裂褶皱。以前的工作表明，细胞骨架蛋白和膜运输协调作用来驱动褶皱内陷，但是这些膜储存来自何处以及如何指导褶皱过程还不太清楚。在这里，我们鉴定了一个广泛的 Rab35/Rab4>Rab39/Klp98A>高尔基网络（TGN）内吞回收途径，该途径对于果蝇胚胎中的快速褶皱内陷是必需的。Rab39 存在于 TGN 的囊泡管状隔室中，通过 Rab35/Rab4 依赖性途径接收内吞作用的货物。Kinesin-3 家族成员 Klp98A 驱动 Rab39 的运动和小管形成活性，并且破坏这种 Rab39-Klp98A-Rab35 途径会导致深褶皱内陷缺陷和基因组不稳定性。这些数据表明，内吞回收途径可以快速从细胞表面重新动员膜货物，并将其引导到高尔基网络，以允许新的分裂褶皱形成循环的启动。
