RRC ID 45595
Author Liu O, Grant BD.
Title Basolateral Endocytic Recycling Requires RAB-10 and AMPH-1 Mediated Recruitment of RAB-5 GAP TBC-2 to Endosomes.
Journal PLoS Genet
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.
Volume 11(9)
Pages e1005514
Published 2015-1-1
DOI 10.1371/journal.pgen.1005514
PMID 26393361
PMC PMC4578947
MeSH Animals Caenorhabditis elegans / genetics Caenorhabditis elegans Proteins / genetics* Caenorhabditis elegans Proteins / metabolism Endocytosis / genetics Endosomes / genetics Endosomes / metabolism GTPase-Activating Proteins / genetics* GTPase-Activating Proteins / metabolism Gene Expression Regulation / genetics Intestinal Mucosa / metabolism Nerve Tissue Proteins / genetics* Nerve Tissue Proteins / metabolism Protein Transport / genetics RNA Interference Vesicular Transport Proteins / genetics* Vesicular Transport Proteins / metabolism rab GTP-Binding Proteins / genetics* rab GTP-Binding Proteins / metabolism
IF 5.175
Times Cited 10
C.elegans tm2241 tm1060