UNC-108/Rab2 regulates postendocytic trafficking in Caenorhabditis elegans.
After endocytosis, membrane proteins are often sorted between two alternative pathways: a recycling pathway and a degradation pathway. Relatively little is known about how trafficking through these alternative pathways is differentially regulated. Here, we identify UNC-108/Rab2 as a regulator of postendocytic trafficking in both neurons and coelomocytes. Mutations in the Caenorhabditis elegans Rab2 gene unc-108, caused the green fluorescent protein (GFP)-tagged glutamate receptor GLR-1 (GLR-1::GFP) to accumulate in the ventral cord and in neuronal cell bodies. In neuronal cell bodies of unc-108/Rab2 mutants, GLR-1::GFP was found in tubulovesicular structures that colocalized with markers for early and recycling endosomes, including Syntaxin-13 and Rab8. GFP-tagged Syntaxin-13 also accumulated in the ventral cord of unc-108/Rab2 mutants. UNC-108/Rab2 was not required for ubiquitin-mediated sorting of GLR-1::GFP into the multivesicular body (MVB) degradation pathway. Mutations disrupting the MVB pathway and unc-108/Rab2 mutations had additive effects on GLR-1::GFP levels in the ventral cord. In coelomocytes, postendocytic trafficking of the marker Texas Red-bovine serum albumin was delayed. These results demonstrate that UNC-108/Rab2 regulates postendocytic trafficking, most likely at the level of early or recycling endosomes, and that UNC-108/Rab2 and the MVB pathway define alternative postendocytic trafficking mechanisms that operate in parallel. These results define a new function for Rab2 in protein trafficking.
Chun
Denise K
DK
Department of Molecular Biology, Massachusetts General Hospital, and Department of Genetics, Harvard Medical School, Boston MA 02114, USA.
McEwen
Jason M
JM
Burbea
Michelle
M
Kaplan
Joshua M
JM
D000818:Animals; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000502:physiology*; D003001:Cloning, Molecular; D004705:Endocytosis; D011992:Endosomes / Q000378:metabolism; D006026:Glycoside Hydrolases / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008954:Models, Biological; D009154:Mutation; D009474:Neurons / Q000378:metabolism; D021381:Protein Transport; D050765:Qa-SNARE Proteins / Q000378:metabolism; D013569:Synapses / Q000378:metabolism; D019076:Transgenes; D020691:rab GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D020693:rab2 GTP-Binding Protein / Q000235:genetics / Q000502:physiology*
D029742:Caenorhabditis elegans Proteins; D050765:Qa-SNARE Proteins; D049452:Green Fluorescent Proteins; D006026:Glycoside Hydrolases; C534960:UNC-108 protein, C elegans; D020691:rab GTP-Binding Proteins; D020693:rab2 GTP-Binding Protein