Coupling of membrane traffic and cytoskeleton remodeling in the regulation of cell motility

细胞运动和细胞分裂受到膜运输和肌动蛋白细胞骨架重塑的协调调节。小GTP酶的Arf和Rab家族调节膜运输，Rho家族小GTP酶调节细胞骨架重塑。在这项研究中，我们发现Arfaptins，这是Arl 1和Rac 1的双重效应，通过与Arl 1相互作用被招募到trans-Golgi膜上，并以Arl 1依赖的方式诱导膜微管化。Arl 1-Arfaptin-2复合物的X-射线晶体结构揭示了Arfaptin-2膜募集的分子基础，并表明Arl 1和Rac 1相互竞争结合Arfaptin-2的可能性。另一方面，我们表明Arf 6在胞质分裂过程中通过与MLKP 1相互作用被募集到弗莱明体，MLKP 1与MgcRacGAP形成复合物，并参与胞质分裂的调节。此外，我们还通过X射线晶体学方法揭示了Arf 6-MKLP 1复合物的结构，并提出了Arf 6募集到Flemming小体的分子基础。我们进一步表明，EFA 6，一个Arf-GEF，参与局部激活的Arf 6在胞质分裂。

Cell motility and cell division are under coordinated regulation of membrane traffic and actin cytoskeleton remodeling. The Arf and Rab families of small GTPases regulate membrane traffic, and the Rho family small GTPases regulate cytoskeleton remodeling. In this study, we showed that Arfaptins, which are dual effectors of Arl1 and Rac1, are recruited onto trans-Golgi membranes through interacting with Arl1, and induce membrane tubulation in an Arl1-dependent manner. X-ray crystal structure of the Arl1-Arfaptin-2 complex revealed the molecular basis for the membrane recruitment of Arfaptin-2 and indicated a possibility that Arl1 and Rac1 compete with each other for binding to Arfaptin-2.On the other hand, we showed that Arf6 is recruited to the Flemming body during cytokinesis through interacting with MLKP1, which forms a complex with MgcRacGAP, and is involved in regulation of cytokinesis. Furthermore, We revealed the structure of the Arf6-MKLP1 complex by X-ray crystallography and suggested the molecular basis for recruitment of Arf6 onto the Flemming body. We further showed that EFA6, an Arf-GEF, is involved in local activation of Arf6 during cytokinesis.