title: GRAB is a binding partner for the Rab11a and Rab11b GTPases.
abstract: Co-ordination of Rab GTPase function has emerged as a crucial mechanism in the control of intracellular trafficking processes in eukaryotic cells. Here, we show that GRAB/Rab3IL1 [guanine nucleotide exchange factor for Rab3A; RAB3A interacting protein (rabin3)-like 1], a protein that has previously be shown to act as a GEF (guanine nucleotide exchange factor) for Rab3a, Rab8a and Rab8b, is also a binding partner for Rab11a and Rab11b, but not the closely related Rab25 GTPase. We demonstrate that exogenous expression of Rab11a and Rab11b shift GRAB's distribution from the cytoplasm onto membranes. We find that the Rab11a/Rab11b-binding region of GRAB lies within its carboxy-terminus, a region distinct from its GEF domain and Rab3a-binding region. Finally, we describe a GRAB deletion mutant (GRABΔ223-228) that is deficient in Rab11-binding ability. These data identify GRAB as a dual Rab-binding protein that could potentially link Rab3 and Rab11 and/or Rab8 and Rab11-mediated intracellular trafficking processes.
authors.affiliation: Molecular Cell Biology Laboratory, School of Biochemistry and Cell Biology, BioSciences Institute, University College Cork, Cork, Ireland. Electronic address: conor.horgan@ucc.ie.
authors.forename: Conor P
authors.initials: CP
authors.lastname: Horgan
authors.forename: Sara R
authors.initials: SR
authors.lastname: Hanscom
authors.forename: Mary W
authors.initials: MW
authors.lastname: McCaffrey
mesh_terms: D000595:Amino Acid Sequence; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D021381:Protein Transport; D020798:Two-Hybrid System Techniques
chemical_list: D020662:Guanine Nucleotide Exchange Factors; D050505:Mutant Proteins; D020558:GTP Phosphohydrolases
keywords: ERC; Effector; GAP; GEF; GRAB; GTPase-activating protein; InsP6K-1; RAB3A interacting protein (rabin3)-like 1; RAB3A-interacting protein; Rab11; Rab25; Rab3IL1; Rab3IP; Rabin8; endosomal-recycling compartment; guanine nucleotide exchange factor; guanine nucleotide exchange factor for Rab3A; inositol hexakisphosphate kinase-1