Rab35: GEFs, GAPs and effectors

Traffic. 2013 Nov;14(11):1109-17. doi: 10.1111/tra.12096. Epub 2013 Aug 21.


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.

Keywords: Arf; DENN domain; DENND; GAP; GEF; GTPase; Rab; Rab35; TBC domain; clathrin-coated vesicle; endosome.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • GTPase-Activating Proteins / chemistry
  • GTPase-Activating Proteins / metabolism*
  • Humans
  • Protein Structure, Tertiary
  • Protein Transport
  • Rho Guanine Nucleotide Exchange Factors / chemistry
  • Rho Guanine Nucleotide Exchange Factors / metabolism*
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / metabolism*


  • GTPase-Activating Proteins
  • Rho Guanine Nucleotide Exchange Factors
  • rab GTP-Binding Proteins