Basolateral Endocytic Recycling Requires RAB-10 and AMPH-1 Mediated Recruitment of RAB-5 GAP TBC-2 to Endosomes

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. © 2015 liu,grant.