一种 Gβγ 效应物，ElmoE，在趋化性过程中将 GPCR 信号转导到肌动蛋白网络。
A Gβγ effector, ElmoE, transduces GPCR signaling to the actin network during chemotaxis.
机构信息
Chemotaxis Signal Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852, USA.
出版信息
Dev Cell. 2012 Jan 17;22(1):92-103. doi: 10.1016/j.devcel.2011.11.007.
Abstract
Activation of G protein-coupled receptors (GPCRs) leads to the dissociation of heterotrimeric G-proteins into Gα and Gβγ subunits, which go on to regulate various effectors involved in a panoply of cellular responses. During chemotaxis, Gβγ subunits regulate actin assembly and migration, but the protein(s) linking Gβγ to the actin cytoskeleton remains unknown. Here, we identified a Gβγ effector, ElmoE in Dictyostelium, and demonstrated that it is required for GPCR-mediated chemotaxis. Remarkably, ElmoE associates with Gβγ and Dock-like proteins to activate the small GTPase Rac, in a GPCR-dependent manner, and also associates with Arp2/3 complex and F-actin. Thus, ElmoE serves as a link between chemoattractant GPCRs, G-proteins and the actin cytoskeleton. The pathway, consisting of GPCR, Gβγ, Elmo/Dock, Rac, and Arp2/3, spatially guides the growth of dendritic actin networks in pseudopods of eukaryotic cells during chemotaxis.
摘要
G 蛋白偶联受体 (GPCRs) 的激活导致异三聚体 G 蛋白解离为 Gα 和 Gβγ 亚基，这些亚基继续调节各种效应物，参与多种细胞反应。在趋化作用过程中，Gβγ 亚基调节肌动蛋白组装和迁移，但将 Gβγ 与肌动蛋白细胞骨架连接的蛋白质仍不清楚。在这里，我们鉴定了盘基网柄菌中的 Gβγ 效应物 ElmoE，并证明它是 GPCR 介导的趋化作用所必需的。值得注意的是，ElmoE 以 GPCR 依赖的方式与 Gβγ 和 Dock 样蛋白结合，激活小 GTPase Rac，还与 Arp2/3 复合物和 F-肌动蛋白结合。因此，ElmoE 充当趋化性 GPCR、G 蛋白和肌动蛋白细胞骨架之间的连接物。该途径由 GPCR、Gβγ、Elmo/Dock、Rac 和 Arp2/3 组成，在趋化作用过程中，在真核细胞的伪足中空间引导树突状肌动蛋白网络的生长。
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