Gumienny T L, Brugnera E, Tosello-Trampont A C, Kinchen J M, Haney L B, Nishiwaki K, Walk S F, Nemergut M E, Macara I G, Francis R, Schedl T, Qin Y, Van Aelst L, Hengartner M O, Ravichandran K S
Cold Spring Harbor Laboratory, 1 Bungtown Road, Cold Spring Harbor, NY 11743, USA.
Cell. 2001 Oct 5;107(1):27-41. doi: 10.1016/s0092-8674(01)00520-7.
The C. elegans genes ced-2, ced-5, and ced-10, and their mammalian homologs crkII, dock180, and rac1, mediate cytoskeletal rearrangements during phagocytosis of apoptotic cells and cell motility. Here, we describe an additional member of this signaling pathway, ced-12, and its mammalian homologs, elmo1 and elmo2. In C. elegans, CED-12 is required for engulfment of dying cells and for cell migrations. In mammalian cells, ELMO1 functionally cooperates with CrkII and Dock180 to promote phagocytosis and cell shape changes. CED-12/ELMO-1 binds directly to CED-5/Dock180; this evolutionarily conserved complex stimulates a Rac-GEF, leading to Rac1 activation and cytoskeletal rearrangements. These studies identify CED-12/ELMO as an upstream regulator of Rac1 that affects engulfment and cell migration from C. elegans to mammals.
秀丽隐杆线虫基因ced - 2、ced - 5和ced - 10及其哺乳动物同源物crkII、dock180和rac1，在凋亡细胞吞噬和细胞运动过程中介导细胞骨架重排。在此，我们描述了该信号通路的另一个成员ced - 12及其哺乳动物同源物elmo1和elmo2。在秀丽隐杆线虫中，CED - 12是死亡细胞吞噬和细胞迁移所必需的。在哺乳动物细胞中，ELMO1与CrkII和Dock180在功能上协同作用，以促进吞噬作用和细胞形态变化。CED - 12/ELMO - 1直接与CED - 5/Dock180结合；这种进化上保守的复合物刺激一种Rac - GEF，导致Rac1激活和细胞骨架重排。这些研究确定CED - 12/ELMO是Rac1的上游调节因子，影响从秀丽隐杆线虫到哺乳动物的吞噬作用和细胞迁移。
