Biology Department, University of Massachusetts, Amherst, United States.
Molecular and Cellular Biology Graduate Program, University of Massachusetts, Amherst, United States.
Elife. 2019 Feb 13;8:e38968. doi: 10.7554/eLife.38968.
Microtubules (MTs) are essential for cleavage furrow positioning during cytokinesis, but the mechanisms by which MT-derived signals spatially define regions of cortical contractility are unresolved. In this study cytokinesis regulators visualized in () cells were found to localize to and track MT plus-ends during cytokinesis. The RhoA GEF Pebble ( ECT2) did not evidently tip-track, but rather localized rapidly to cortical sites contacted by MT plus-tips, resulting in RhoA activation and enrichment of myosin-regulatory light chain. The MT plus-end localization of centralspindlin was compromised following EB1 depletion, which resulted in a higher incidence of cytokinesis failure. Centralspindlin plus-tip localization depended on the C-terminus and a putative EB1-interaction motif (hxxPTxh) in RacGAP50C. We propose that MT plus-end-associated centralspindlin recruits a cortical pool of ECT2 upon physical contact to activate RhoA and to trigger localized contractility.
微管（MTs）对于胞质分裂期间的分裂沟定位至关重要，但 MT 衍生信号如何在空间上限定皮质收缩性区域的机制尚不清楚。在这项研究中，发现胞质分裂调节剂在 () 细胞中定位于并跟踪胞质分裂期间的 MT 正极。RhoA GEF 卵石（ECT2）显然没有尖端跟踪，而是快速定位于 MT 正极接触的皮质部位，导致 RhoA 激活和肌球蛋白调节轻链的富集。EB1 耗竭后，中心纺锤体的 MT 正极定位受损，导致胞质分裂失败的发生率更高。中央纺锤体正极定位取决于 RacGAP50C 中的 C 末端和假定的 EB1 相互作用基序（hxxPTxh）。我们提出，与物理接触的 MT 正极相关的中心纺锤体募集皮质池中的 ECT2，以激活 RhoA 并触发局部收缩性。
