Rabex-5 determines the neurite localization of its downstream Rab proteins in hippocampal neurons

Rab family small GTPases function as molecular switches in the regulation of membrane traffic, and their activity is thought to be controlled by guanine nucleotide exchange factors (GEFs). However, the role of GEFs in targeting Rab proteins to specific membrane compartments is poorly understood. We have recently reported finding that Rabex-5, originally described as a Rab5-GEF, also functions as a Rab17-GEF in mouse hippocampal neurons. The Rab17 in developing hippocampal neurons is specifically targeted to their dendrites and not to their axons, and the GEF activity of Rabex-5 is required for translocation of Rab17 from the cell body to the dendrites. Interestingly, Rabex-5 is also required for the axon and dendrite localization of Rab5 and Rab21 in hippocampal neurons. Our findings indicate that Rabex-5 determines the targeting of its downstream Rab proteins to the dendrites (Rab17) or to both the axon and dendrites (Rab5 and Rab21).