title: Rab35: GEFs, GAPs and effectors.
abstract: Rabs are the largest family of small GTPases and are master regulators of membrane trafficking. Following activation by guanine-nucleotide exchange factors (GEFs), each Rab binds a specific set of effector proteins that mediate the various downstream functions of that Rab. Then, with the help of GTPase-activating proteins, the Rab converts GTP to GDP, terminating its function. There are over 60 Rabs in humans and only a subset has been analyzed in any detail. Recently, Rab35 has emerged as a key regulator of cargo recycling at endosomes, with an additional role in regulation of the actin cytoskeleton. Here, we will focus on the regulation of Rab35 activity by the connecdenn/DENND1 family of GEFs and the TBC1D10/EPI64 family of GTPase-activating proteins. We will describe how analysis of these proteins, as well as a plethora of Rab35 effectors has provided insights into Rab35 function. Finally, we will describe how Rab35 provides a novel link between the Rab and Arf family of GTPases with implications for tumor formation and invasiveness.
authors.affiliation: Department of Neurology and Neurosurgery, Montreal Neurological Institute, McGill University, Montreal, Quebec, H3A 2B4, Canada.
authors.forename: Mathilde
authors.initials: M
authors.lastname: Chaineau
authors.forename: Maria S
authors.initials: MS
authors.lastname: Ioannou
authors.forename: Peter S
authors.initials: PS
authors.lastname: McPherson
mesh_terms: D000818:Animals; D020690:GTPase-Activating Proteins / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D064067:Rho Guanine Nucleotide Exchange Factors / Q000737:chemistry / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: D020690:GTPase-Activating Proteins; D064067:Rho Guanine Nucleotide Exchange Factors; D020691:rab GTP-Binding Proteins
keywords: Arf; DENN domain; DENND; GAP; GEF; GTPase; Rab; Rab35; TBC domain; clathrin-coated vesicle; endosome