Cdc42 GTPase activating proteins Rga4 and Rga6 coordinate septum synthesis and membrane trafficking at the division plane during cytokinesis
Cdc42 GTPase activating proteins Rga4 and Rga6 coordinate septum synthesis and membrane trafficking at the division plane during cytokinesis
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DOI：
10.1111/tra.12864
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发表时间：
2022-09-06
期刊：
影响因子：
4.5
通讯作者：
Das，Maitreyi E.
中科院分区：
文献类型：
--
作者：
Campbell，Bethany F.;Hercyk，Brian S.;Das，Maitreyi E.
裂殖酵母胞质分裂是由同时进行的隔膜合成、膜开沟和肌动球蛋白环收缩驱动的。隔膜由一个初级隔膜和两侧的次级隔膜组成。首先，葡聚糖合酶Bgs 1和膜囊泡的递送启动初级隔膜合成和开沟。接下来，递送Bgs 4用于二次隔膜形成。目前还不清楚隔膜合成是如何与膜开沟协调的。Cdc42促进Bgs 1的递送，但不促进Bgs 4的递送。我们发现，初级隔膜启动后，Cdc42灭活Rga 4和Rga 6本地化的分裂网站。Inrga 4 Δ rga 6 Δ突变体，Cdc42活性在后期胞质分裂期间增强，并且细胞需要更长的时间分离。这些突变体分裂部位的电子显微镜照片显示畸形的隔膜和不规则的膜结构。这些突变体具有更大的分裂平面，具有增强的Bgs1递送，但不能增强Bgs4和几种胞外蛋白的积累。此外，这些突变体在分裂位点显示出内吞缺陷。这表明Cdc42调节初级隔膜形成和仅某些膜运输事件。随着胞质分裂的进行，Rga 4和Rga 6定位于分裂位点以降低Cdc42活性，从而允许Cdc42独立的膜运输事件与隔膜形成偶联，以获得适当的隔膜形态。
Fission yeast cytokinesis is driven by simultaneous septum synthesis, membrane furrowing and actomyosin ring constriction. The septum consists of a primary septum flanked by secondary septa. First, delivery of the glucan synthase Bgs1 and membrane vesicles initiate primary septum synthesis and furrowing. Next, Bgs4 is delivered for secondary septum formation. It is unclear how septum synthesis is coordinated with membrane furrowing. Cdc42 promotes delivery of Bgs1 but not Bgs4. We find that after primary septum initiation, Cdc42 inactivators Rga4 and Rga6 localize to the division site. Inrga4Δrga6Δmutants, Cdc42 activity is enhanced during late cytokinesis and cells take longer to separate. Electron micrographs of the division site in these mutants exhibit malformed septum with irregular membrane structures. These mutants have a larger division plane with enhanced Bgs1 delivery but fail to enhance accumulation of Bgs4 and several exocytic proteins. Additionally, these mutants show endocytic defects at the division site. This suggests that Cdc42 regulates primary septum formation and only certain membrane trafficking events. As cytokinesis progresses Rga4 and Rga6 localize to the division site to decrease Cdc42 activity to allow coupling of Cdc42‐independent membrane trafficking events with septum formation for proper septum morphology.