Pinar Mario, Alonso Ana, de Los Ríos Vivian, Bravo-Plaza Ignacio, de la Gandara Álvaro, Galindo Antonio, Arias-Palomo Ernesto, Peñalva Miguel Á
Department of Cellular and Molecular Biology, Centro de Investigaciones Biológicas CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
Proteomics Facility, Centro de Investigaciones Biológicas CSIC, Ramiro de Maeztu 9, 28040 Madrid, Spain.
iScience. 2022 Jun 2;25(7):104514. doi: 10.1016/j.isci.2022.104514. eCollection 2022 Jul 15.
In the apex-directed RAB11 exocytic pathway of , kinesin-1/KinA conveys secretory vesicles (SVs) to the hyphal tip, where they are transferred to the type V myosin MyoE. MyoE concentrates SVs at an apical store located underneath the PM resembling the presynaptic active zone. A rod-shaped RAB11 effector, UDS1, and the intrinsically disordered and coiled-coil HMSV associate with MyoE in a stable HUM (HMSV-UDS1-MyoE) complex recruited by RAB11 to SVs through an interaction network involving RAB11 and HUM components, with the MyoE globular tail domain (GTD) binding both HMSV and RAB11-GTP and RAB11-GTP binding both the MyoE-GTD and UDS1. UDS1 bridges RAB11-GTP to HMSV, an avid interactor of the MyoE-GTD. The interaction between the UDS1-HMSV sub-complex and RAB11-GTP can be reconstituted . Ablating UDS1 or HMSV impairs actomyosin-mediated transport of SVs to the apex, resulting in spreading of RAB11 SVs across the apical dome as KinA/microtubule-dependent transport gains prominence.
在RAB11向菌丝顶端的胞吐途径中，驱动蛋白-1/KinA将分泌囊泡（SVs）转运至菌丝顶端，在那里它们被转移至V型肌球蛋白MyoE。MyoE将SVs聚集在质膜下方的顶端储存区，该区域类似于突触前活性区。一种杆状RAB11效应蛋白UDS1以及内在无序且呈卷曲螺旋结构的HMSV与MyoE结合，形成稳定的HUM（HMSV-UDS1-MyoE）复合物，该复合物由RAB11通过一个涉及RAB11和HUM组分的相互作用网络招募至SVs，其中MyoE球状尾部结构域（GTD）同时结合HMSV和RAB11-GTP，且RAB11-GTP同时结合MyoE-GTD和UDS1。UDS1将RAB11-GTP与HMSV连接起来，HMSV是MyoE-GTD的一个活跃相互作用因子。UDS1-HMSV亚复合物与RAB11-GTP之间的相互作用可以被重建。敲除UDS1或HMSV会损害肌动球蛋白介导的SVs向顶端的运输，导致随着KinA/微管依赖性运输变得突出，RAB11 SVs在顶端穹顶扩散。
