Department of Biomedical Sciences, University of Lausanne, Lausanne, Switzerland.
Laboratory of Membrane Trafficking Mechanisms, Department of Integrative Life Sciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi, Japan.
Cell Rep. 2021 Nov 2;37(5):109945. doi: 10.1016/j.celrep.2021.109945.
Endocytosis and endosome dynamics are controlled by proteins of the small GTPase Rab family. Besides possible recycling routes to the plasma membrane and various organelles, previously described endocytic pathways (e.g., clathrin-mediated endocytosis, macropinocytosis, CLIC/GEEC pathway) all appear to funnel the endocytosed material to Rab5-positive early endosomes that then mature into Rab7-positive late endosomes/lysosomes. By studying the uptake of a series of cell-penetrating peptides (CPPs), we identify an endocytic pathway that moves material to nonacidic Lamp1-positive late endosomes. Trafficking via this endocytic route is fully independent of Rab5 and Rab7 but requires the Rab14 protein. The pathway taken by CPPs differs from the conventional Rab5-dependent endocytosis at the stage of vesicle formation already, as it is not affected by a series of compounds that inhibit macropinocytosis or clathrin-mediated endocytosis. The Rab14-dependent pathway is also used by physiological cationic molecules such as polyamines and homeodomains found in homeoproteins.
内吞作用和内体动力学受小 GTPase Rab 家族蛋白的控制。除了可能的再循环途径到质膜和各种细胞器，以前描述的内吞途径（例如，网格蛋白介导的内吞作用、巨胞饮作用、CLIC/GEEC 途径）似乎都将内吞的物质引导到 Rab5 阳性早期内体，然后成熟为 Rab7 阳性晚期内体/溶酶体。通过研究一系列细胞穿透肽（CPPs）的摄取，我们确定了一种将物质转移到非酸性 Lamp1 阳性晚期内体的内吞途径。通过这种内吞途径的运输完全独立于 Rab5 和 Rab7，但需要 Rab14 蛋白。CPPs 所走的途径与传统的 Rab5 依赖性内吞作用在囊泡形成阶段已经不同，因为它不受一系列抑制巨胞饮作用或网格蛋白介导的内吞作用的化合物的影响。Rab14 依赖性途径也被生理阳离子分子如多胺和同源域所利用，这些分子存在于同源蛋白中。
