Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Aobayama, Aoba-ku, Sendai, Miyagi, 980-8578, Japan.
Biochem Biophys Res Commun. 2021 Jul 5;561:151-157. doi: 10.1016/j.bbrc.2021.05.009. Epub 2021 May 21.
Rab small GTPases regulate intracellular membrane trafficking by interacting with specific binding proteins called Rab effectors. Although Rab6 is implicated in basement membrane formation and secretory cargo trafficking, its precise regulatory mechanisms have remained largely unknown. In the present study we established five knockout cell lines for candidate Rab6 effectors and discovered that knockout of VPS52, a subunit of the GARP complex, resulted in attenuated secretion and lysosomal accumulation of secretory cargos, the same as Rab6-knockout does. We also evaluated the functional importance of the previously uncharacterized C-terminal region of VPS52 for restoring these phenotypes, as well as for the sorting of lysosomal proteins. Our findings suggest that VPS52 is an effector protein that is responsible for the Rab6-dependent secretory cargo trafficking.
Rab 小分子 GTPases 通过与称为 Rab 效应物的特定结合蛋白相互作用来调节细胞内的膜运输。虽然 Rab6 参与基底膜形成和分泌货物运输，但它的精确调节机制在很大程度上仍然未知。在本研究中，我们建立了五个候选 Rab6 效应物的敲除细胞系，发现 GARP 复合物的一个亚基 VPS52 的敲除导致分泌减少和分泌货物的溶酶体积累，与 Rab6 敲除的效果相同。我们还评估了 VPS52 的以前未表征的 C 末端区域对于恢复这些表型以及溶酶体蛋白的分选的功能重要性。我们的研究结果表明，VPS52 是一种效应蛋白，负责 Rab6 依赖性分泌货物运输。
