CED-10/Rac1 regulates endocytic recycling through the RAB-5 GAP TBC-2.
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.
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
Lin
L
Sun
Ou
O
Liu
Jigar
J
Desai
Farhad
F
Karbassi
Marc-André
MA
Sylvain
Anbing
A
Shi
Zheng
Z
Zhou
Christian E
CE
Rocheleau
Barth D
BD
Grant
D000818:Animals; D051017:Apoptosis Regulatory Proteins; D017173:Caenorhabditis elegans / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D003598:Cytoskeletal Proteins / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics / Q000502:physiology; D011992:Endosomes / Q000378:metabolism / Q000502:physiology; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D007413:Intestinal Mucosa / Q000378:metabolism; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010587:Phagocytosis / Q000235:genetics; D021381:Protein Transport; D015398:Signal Transduction; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism; D020744:rac GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism
D051017:Apoptosis Regulatory Proteins; C407268:CED-10 protein, C elegans; C438369:CED-12 protein, C elegans; C111579:CED-5 protein, C elegans; D029742:Caenorhabditis elegans Proteins; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D020690:GTPase-Activating Proteins; D008565:Membrane Proteins; C558452:Rab-5 protein, C elegans; C559069:TBC-2 protein, C elegans; D033921:Vesicular Transport Proteins; D020744:rac GTP-Binding Proteins