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CED-10/Rac1 通过 RAB-5 GAP TBC-2 调节内吞回收。

CED-10/Rac1 regulates endocytic recycling through the RAB-5 GAP TBC-2.

机构信息

Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.

出版信息

PLoS Genet. 2012;8(7):e1002785. doi: 10.1371/journal.pgen.1002785. Epub 2012 Jul 12.

DOI:10.1371/journal.pgen.1002785
PMID:22807685
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3395619/
Abstract

Rac1 is a founding member of the Rho-GTPase family and a key regulator of membrane remodeling. In the context of apoptotic cell corpse engulfment, CED-10/Rac1 acts with its bipartite guanine nucleotide exchange factor, CED-5/Dock180-CED-12/ELMO, in an evolutionarily conserved pathway to promote phagocytosis. Here we show that in the context of the Caenorhabditis elegans intestinal epithelium CED-10/Rac1, CED-5/Dock180, and CED-12/ELMO promote basolateral recycling. Furthermore, we show that CED-10 binds to the RAB-5 GTPase activating protein TBC-2, that CED-10 contributes to recruitment of TBC-2 to endosomes, and that recycling cargo is trapped in recycling endosomes in ced-12, ced-10, and tbc-2 mutants. Expression of GTPase defective RAB-5(Q78L) also traps recycling cargo. Our results indicate that down-regulation of early endosome regulator RAB-5/Rab5 by a CED-5, CED-12, CED-10, TBC-2 cascade is an important step in the transport of cargo through the basolateral recycling endosome for delivery to the plasma membrane.

摘要

Rac1 是 Rho-GTPase 家族的创始成员之一，也是膜重塑的关键调节因子。在凋亡细胞尸骸吞噬的背景下，CED-10/Rac1 与其二聚体鸟嘌呤核苷酸交换因子 CED-5/Dock180-CED-12/ELMO 一起作用，在进化上保守的途径中促进吞噬作用。在这里，我们表明在秀丽隐杆线虫肠道上皮细胞中，CED-10/Rac1、CED-5/Dock180 和 CED-12/ELMO 促进基底外侧循环。此外，我们表明 CED-10 与 RAB-5 GTP 酶激活蛋白 TBC-2 结合，CED-10 有助于将 TBC-2 募集到内体，并且在 ced-12、ced-10 和 tbc-2 突变体中循环货物被捕获在循环内体中。表达 GTPase 缺陷型 RAB-5(Q78L)也会捕获循环货物。我们的结果表明，CED-5、CED-12、CED-10、TBC-2 级联下调早期内体调节剂 RAB-5/Rab5 是货物通过基底外侧循环内体运输到质膜的重要步骤。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/d4c0e006fec9/pgen.1002785.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/b2f708926047/pgen.1002785.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/58e1d996ebc2/pgen.1002785.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/a01c5500d3c8/pgen.1002785.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/bf428e13fdf4/pgen.1002785.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/fde614eb3f82/pgen.1002785.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/d4c0e006fec9/pgen.1002785.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/b2f708926047/pgen.1002785.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/58e1d996ebc2/pgen.1002785.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/a01c5500d3c8/pgen.1002785.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/bf428e13fdf4/pgen.1002785.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/fde614eb3f82/pgen.1002785.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/df23/3395619/d4c0e006fec9/pgen.1002785.g006.jpg

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