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CED-10/Rac1 regulates endocytic recycling through the RAB-5 GAP TBC-2.
- Source :
-
PLoS genetics [PLoS Genet] 2012; Vol. 8 (7), pp. e1002785. Date of Electronic Publication: 2012 Jul 12. - Publication Year :
- 2012
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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.<br />Competing Interests: The authors have declared that no competing interests exist.
- Subjects :
- Animals
Apoptosis Regulatory Proteins
Carrier Proteins metabolism
Cell Membrane metabolism
Cytoskeletal Proteins metabolism
Endosomes metabolism
Endosomes physiology
Gene Expression Regulation
Intestinal Mucosa metabolism
Membrane Proteins genetics
Membrane Proteins metabolism
Mutation
Phagocytosis genetics
Protein Transport
Signal Transduction
Caenorhabditis elegans genetics
Caenorhabditis elegans metabolism
Caenorhabditis elegans physiology
Caenorhabditis elegans Proteins genetics
Caenorhabditis elegans Proteins metabolism
Endocytosis genetics
Endocytosis physiology
GTPase-Activating Proteins genetics
GTPase-Activating Proteins metabolism
Vesicular Transport Proteins genetics
Vesicular Transport Proteins metabolism
rac GTP-Binding Proteins genetics
rac GTP-Binding Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1553-7404
- Volume :
- 8
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PLoS genetics
- Publication Type :
- Academic Journal
- Accession number :
- 22807685
- Full Text :
- https://doi.org/10.1371/journal.pgen.1002785