City University of Hong Kong Shenzhen Research Institute, Shenzhen, China.
Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.
Elife. 2021 Nov 19;10:e65910. doi: 10.7554/eLife.65910.
Actin filaments (F-actin) have been implicated in various steps of endosomal trafficking, and the length of F-actin is controlled by actin capping proteins, such as CapZ, which is a stable heterodimeric protein complex consisting of α and β subunits. However, the role of these capping proteins in endosomal trafficking remains elusive. Here, we found that CapZ docks to endocytic vesicles via its C-terminal actin-binding motif. CapZ knockout significantly increases the F-actin density around immature early endosomes, and this impedes fusion between these vesicles, manifested by the accumulation of small endocytic vesicles in CapZ-knockout cells. CapZ also recruits several RAB5 effectors, such as Rabaptin-5 and Rabex-5, to RAB5-positive early endosomes via its N-terminal domain, and this further activates RAB5. Collectively, our results indicate that CapZ regulates endosomal trafficking by controlling actin density around early endosomes and recruiting RAB5 effectors.
肌动蛋白丝（F-actin）参与了各种内体运输步骤，并且 F-actin 的长度受到肌动蛋白加帽蛋白的控制，例如 CapZ，它是由α和β亚基组成的稳定异源二聚体蛋白复合物。然而，这些加帽蛋白在内体运输中的作用仍然难以捉摸。在这里，我们发现 CapZ 通过其 C 末端肌动蛋白结合基序与内吞小泡结合。CapZ 敲除显著增加了不成熟早期内体周围的 F-actin 密度，这阻碍了这些小泡之间的融合，表现在 CapZ 敲除细胞中积累了小的内吞小泡。CapZ 还通过其 N 端结构域将几种 RAB5 效应物，如 Rabaptin-5 和 Rabex-5，招募到 RAB5 阳性早期内体上，从而进一步激活 RAB5。总的来说，我们的结果表明，CapZ 通过控制早期内体周围的肌动蛋白密度和招募 RAB5 效应物来调节内体运输。
