REI-1, a Novel Rab11 GEF with a SH3BP5 domain

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.

Differential interactions of missing in metastasis and insulin receptor tyrosine kinase substrate with RAB proteins in the endocytosis of CXCR4

“…Another possibility is that the SH3 domain facilitates interaction with RAB11 by linking to an unknown intracellular protein that regulates RAB11. In this regard, it is worth noting that SH3BP5 (also REI-I), a newly identified GEF of RAB11, is an SH3 binding protein and contains an F-BAR domain (38). Whether the link to actin assembly or an RAB11 GEF is responsible for the selective interaction of IRTKS with RAB11 requires further investigation.…”

Mitochondrial P-JNK target, SAB (SH3BP5), in regulation of cell death

“…The N-terminus of SAB is speculated to have four coiled-coil domains, and SAB is a homolog of Ras-related GTP-binding protein Rab11 (RAB-11)-interacting protein-1 (REI-1) and a guanine nucleotide exchange factor (GEF) of Citrobacter elegans; however, both SAB and REI-1 do not contain any known Rab-GEF domain. REI-1 is expressed in C. elegans germline and co-localizes with small guanosine triphosphate hydrolase (GTPases) RAB-11 on the late-Golgi membranes (Sakaguchi et al, 2015;Sakaguchi et al, 2016;Sato et al, 2016). Given this, the structural analysis revealed the Rab-11 binding site on both helix α1 and α4 of murine SH3BP5 and REI-1 of C. elegans (Jenkins et al, 2018).…”