Abstract
The small GTPase Rab proteins are key regulators of membrane trafficking. Rab11 is one of the best-characterized molecules among the Rab family proteins and it plays multiple roles in endocytic recycling, exocytosis, and cytokinesis. However, it remains unclear how Rab11 is activated at a precise timing and location and regulates its diverse functions. Specifically, our knowledge of the upstream regulatory factors that activate Rab11 is limited. In this regard, we have identified the RAB-11-interacting protein-1 (REI-1) as a novel guanine nucleotide exchange factor (GEF) for RAB-11 in Caenorhabditis elegans (C. elegans). REI-1 family proteins are conserved among metazoans, and its human homolog, SH3BP5, also exhibits strong GEF activity toward human Rab11. In C. elegans, REI-1 is expressed in the germline and co-localizes with RAB-11 on late-Golgi membranes. The loss of REI-1 impaired the targeting of RAB-11 to the late-Golgi compartment, as well as the recycling endosomes in embryos and further reduced the recruitment of RAB-11 to the cleavage furrow, resulting in the delay of cytokinesis. We suggest that REI-1 is the GEF responsible for regulating RAB-11 localization and function in early embryos.