Gibieža Paulius, Peterman Eric, Hoffman Huxley K, Van Engeleburg Schuyler, Skeberdis Vytenis Arvydas, Prekeris Rytis
Laboratory of Cell Culture, Institute of Cardiology, Lithuanian University of Health Sciences, Kaunas LT-50162, Lithuania.
Department of Cell and Developmental Biology, University of Colorado Anschutz Medical, Campus, Aurora, CO 80045.
Mol Biol Cell. 2021 Apr 1;32(7):554-566. doi: 10.1091/mbc.E20-09-0607. Epub 2021 Feb 10.
Abscission is a complex cellular process that is required for mitotic division. It is well established that coordinated and localized changes in actin and microtubule dynamics are vital for cytokinetic ring formation, as well as establishment of the abscission site. Actin cytoskeleton reorganization during abscission would not be possible without the interplay between Rab11- and Rab35-containing endosomes and their effector proteins, whose roles in regulating endocytic pathways at the cleavage furrow have now been studied extensively. Here, we identified Rab14 as a novel regulator of cytokinesis. We demonstrate that depletion of Rab14 causes either cytokinesis failure or significantly prolongs division time. We show that Rab14 contributes to the efficiency of recruiting Rab11-endosomes to the thin intracellular bridge (ICB) microtubules and that Rab14 knockout leads to inhibition of actin clearance at the abscission site. Finally, we demonstrate that Rab14 binds to microtubule minus-end interacting MACF2/CAMSAP3 complex and that this binding affects targeting of endosomes to the ICB microtubules. Collectively, our data identified Rab14 and MACF2/CAMSAP3 as proteins that regulate actin depolymerization and endosome targeting during cytokinesis.
细胞分裂后期是有丝分裂所必需的复杂细胞过程。众所周知，肌动蛋白和微管动力学的协调和局部变化对于胞质分裂环的形成以及分裂后期位点的建立至关重要。如果没有含Rab11和Rab35的内体与其效应蛋白之间的相互作用，细胞分裂后期肌动蛋白细胞骨架的重组将无法实现，目前已对它们在调节分裂沟处内吞途径中的作用进行了广泛研究。在此，我们鉴定出Rab14是胞质分裂的新型调节因子。我们证明，Rab14的缺失会导致胞质分裂失败或显著延长分裂时间。我们表明，Rab14有助于将Rab11内体招募到细的细胞内桥（ICB）微管的效率，并且Rab14基因敲除会导致分裂后期位点处肌动蛋白清除的抑制。最后，我们证明Rab14与微管负端相互作用的MACF2/CAMSAP3复合物结合，并且这种结合会影响内体靶向ICB微管。总的来说，我们的数据鉴定出Rab14和MACF2/CAMSAP3是在胞质分裂过程中调节肌动蛋白解聚和内体靶向的蛋白质。
