RAB-10 is required for endocytic recycling in the Caenorhabditis elegans intestine.
The endocytic pathway of eukaryotes is essential for the internalization and trafficking of macromolecules, fluid, membranes, and membrane proteins. One of the most enigmatic aspects of this process is endocytic recycling, the return of macromolecules (often receptors) and fluid from endosomes to the plasma membrane. We have previously shown that the EH-domain protein RME-1 is a critical regulator of endocytic recycling in worms and mammals. Here we identify the RAB-10 protein as a key regulator of endocytic recycling upstream of RME-1 in polarized epithelial cells of the Caenorhabditis elegans intestine. rab-10 null mutant intestinal cells accumulate abnormally abundant RAB-5-positive early endosomes, some of which are enlarged by more than 10-fold. Conversely most RME-1-positive recycling endosomes are lost in rab-10 mutants. The abnormal early endosomes in rab-10 mutants accumulate basolaterally recycling transmembrane cargo molecules and basolaterally recycling fluid, consistent with a block in basolateral transport. These results indicate a role for RAB-10 in basolateral recycling upstream of RME-1. We found that a functional GFP-RAB-10 reporter protein is localized to endosomes and Golgi in wild-type intestinal cells consistent with a direct role for RAB-10 in this transport pathway.
Chen
Carlos Chih-Hsiung
CC
Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA.
Schweinsberg
Peter J
PJ
Vashist
Shilpa
S
Mareiniss
Darren P
DP
Lambie
Eric J
EJ
Grant
Barth D
BD
D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism*; D004705:Endocytosis / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000166:cytology*; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D021381:Protein Transport; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D016415:Sequence Alignment; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*; D020696:rab5 GTP-Binding Proteins / Q000378:metabolism
D029742:Caenorhabditis elegans Proteins; C486205:RME-1 protein, C elegans; D011993:Recombinant Fusion Proteins; C510977:RAB-10 protein, C elegans; D020691:rab GTP-Binding Proteins; D020696:rab5 GTP-Binding Proteins