title: Basolateral Endocytic Recycling Requires RAB-10 and AMPH-1 Mediated Recruitment of RAB-5 GAP TBC-2 to Endosomes.
abstract: The small GTPase RAB-5/Rab5 is a master regulator of the early endosome, required for a myriad of coordinated activities, including the degradation and recycling of internalized cargo. Here we focused on the recycling function of the early endosome and the regulation of RAB-5 by GAP protein TBC-2 in the basolateral C. elegans intestine. We demonstrate that downstream basolateral recycling regulators, GTPase RAB-10/Rab10 and BAR domain protein AMPH-1/Amphiphysin, bind to TBC-2 and help to recruit it to endosomes. In the absence of RAB-10 or AMPH-1 binding to TBC-2, RAB-5 membrane association is abnormally high and recycling cargo is trapped in early endosomes. Furthermore, the loss of TBC-2 or AMPH-1 leads to abnormally high spatial overlap of RAB-5 and RAB-10. Taken together our results indicate that RAB-10 and AMPH-1 mediated down-regulation of RAB-5 is an important step in recycling, required for cargo exit from early endosomes and regulation of early endosome-recycling endosome interactions.
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Ou
authors.initials: O
authors.lastname: Liu
authors.affiliation: Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, New Jersey, United States of America.
authors.forename: Barth D
authors.initials: BD
authors.lastname: Grant
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000235:genetics; D029742:Caenorhabditis elegans Proteins / Q000235:genetics* / Q000378:metabolism; D004705:Endocytosis / Q000235:genetics; D011992:Endosomes / Q000235:genetics / Q000378:metabolism; D020690:GTPase-Activating Proteins / Q000235:genetics* / Q000378:metabolism; D005786:Gene Expression Regulation / Q000235:genetics; D007413:Intestinal Mucosa / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D021381:Protein Transport / Q000235:genetics; D034622:RNA Interference; D033921:Vesicular Transport Proteins / Q000235:genetics* / Q000378:metabolism; D020691:rab GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D029742:Caenorhabditis elegans Proteins; D020690:GTPase-Activating Proteins; D009419:Nerve Tissue Proteins; C558452:Rab-5 protein, C elegans; C559069:TBC-2 protein, C elegans; D033921:Vesicular Transport Proteins; C075637:amphiphysin; C510977:RAB-10 protein, C elegans; D020691:rab GTP-Binding Proteins