Department of Molecular Biosciences, Northwestern University, Evanston, IL.
Department of Molecular Biosciences, Northwestern University, Evanston, IL
J Cell Biol. 2019 Jan 7;218(1):150-170. doi: 10.1083/jcb.201805100. Epub 2018 Nov 19.
Eukaryotic cell division requires dependency relationships in which late processes commence only after early ones are appropriately completed. We have discovered a system that blocks late events of cytokinesis until early ones are successfully accomplished. In budding yeast, cytokinetic actomyosin ring contraction and membrane ingression are coupled with deposition of an extracellular septum that is selectively degraded in its primary septum immediately after its completion by secreted enzymes. We find this secretion event is linked to septum completion and forestalled when the process is slowed. Delay of septum degradation requires Fir1, an intrinsically disordered protein localized to the cytokinesis site that is degraded upon septum completion but stabilized when septation is aberrant. Fir1 protects cytokinesis in part by inhibiting a separation-specific exocytosis function of the NDR/LATS kinase Cbk1, a key component of "hippo" signaling that induces mother-daughter separation. We term this system enforcement of cytokinesis order, a checkpoint ensuring proper temporal sequence of mechanistically incompatible processes of cytokinesis.
真核细胞分裂需要依赖关系，只有在早期过程适当地完成之后，晚期过程才能开始。我们发现了一个系统，它可以阻止胞质分裂的晚期事件，直到早期事件成功完成。在出芽酵母中，胞质分裂肌动球蛋白环收缩和膜内陷与细胞外隔膜的沉积耦合，该隔膜在其完成后立即被分泌酶选择性降解。我们发现，这个分泌事件与隔膜的完成有关，当过程变慢时，它会被阻止。隔膜降解的延迟需要 Fir1，这是一种固有无序的蛋白质，定位于胞质分裂位点，在隔膜完成后降解，但在隔膜异常时稳定。Fir1 通过抑制 NDR/LATS 激酶 Cbk1 的分离特异性胞吐作用来保护胞质分裂，Cbk1 是“hippo”信号的关键组成部分，它诱导母-子分离。我们将这个系统称为胞质分裂秩序的执行，这是一个检查点，确保胞质分裂的机械上不相容过程的适当时间顺序。
