Cascone Ilaria, Selimoglu Rasim, Ozdemir Cafer, Del Nery Elaine, Yeaman Charles, White Michael, Camonis Jacques
Institut Curie, Paris, France.
EMBO J. 2008 Sep 17;27(18):2375-87. doi: 10.1038/emboj.2008.166. Epub 2008 Aug 28.
The Ras family G-proteins RalA and RalB make critical non-overlapping contributions to the generation of a tumorigenic regulatory network, supporting bypass of the normal restraints on both cell proliferation and survival. The Sec6/8 complex, or exocyst, has emerged as a principal direct effector complex for Ral GTPases. Here, we show that RalA and RalB support mitotic progression through mobilization of the exocyst for two spatially and kinetically distinct steps of cytokinesis. RalA is required to tether the exocyst to the cytokinetic furrow in early cytokinesis. RalB is then required for recruitment of the exocyst to the midbody of this bridge to drive abscission and completion of cytokinesis. The collaborative action of RalA and RalB is specified by discrete subcellular compartmentalization and unique pairs of RalGEF proteins that provide inputs from both Ras-family protein-dependent and protein-independent regulatory cues. This suggests that Ral GTPases integrate diverse upstream signals to choreograph multiple roles for the exocyst in mitotic progression.
Ras家族G蛋白RalA和RalB对致瘤调控网络的形成起着关键的非重叠作用，支持细胞增殖和存活中正常限制的绕过。Sec6/8复合体，即外泌体，已成为Ral GTP酶的主要直接效应复合体。在此，我们表明RalA和RalB通过在细胞分裂的两个空间和动力学上不同的步骤中动员外泌体来支持有丝分裂进程。在早期细胞分裂中，RalA是将外泌体拴系到细胞分裂沟所必需的。然后，RalB是将外泌体招募到该桥的中体以驱动分裂和细胞分裂完成所必需的。RalA和RalB的协同作用由离散的亚细胞区室化和独特的RalGEF蛋白对指定，这些蛋白对提供来自Ras家族蛋白依赖性和蛋白非依赖性调控线索的输入。这表明Ral GTP酶整合多种上游信号，为外泌体在有丝分裂进程中编排多种作用。
