The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7
The endocytic pathway taken by cationic substances requires Rab14 but not Rab5 and Rab7
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DOI：
10.1016/j.celrep.2021.109945
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发表时间：
2021-11-02
期刊：
影响因子：
8.8
通讯作者：
Widmann，Christian
中科院分区：
文献类型：
--
作者：
Trofimenko，Evgeniya;Homma，Yuta;Widmann，Christian
内吞作用和内体动力学由小GTTRab家族的蛋白质控制。除了可能的再循环途径到质膜和各种细胞器之外，先前描述的内吞途径（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汇集到Rab 5阳性早期内体，然后成熟为Rab 7阳性晚期内体/溶酶体。通过研究一系列的细胞穿透肽（CPPs）的摄取，我们确定了一个内吞途径，将材料移动到非酸性Lamp 1阳性晚期内体。通过这种内吞途径的运输完全不依赖于Rab 5和Rab 7，但需要Rab 14蛋白。CPPs所采取的途径与囊泡形成阶段的常规Rab 5依赖性内吞作用不同，因为它不受一系列抑制巨胞饮或网格蛋白介导的内吞作用的化合物的影响。Rab 14依赖性途径也被生理阳离子分子如多胺和同源异型蛋白中发现的同源异型结构域使用。
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.