title: New insights in the regulation of Rab GTPases by G protein-coupled receptors.
abstract: Cargo-mediated regulation of vesicular transport has received great attention lately. Rab GTPases, forming the largest branch of the Ras GTPase superfamily, regulate almost every step of vesicle-mediated trafficking. Growing evidence suggests that mutations, aberrant expression, and altered post-translational modifications of Rab GTPases are associated with human diseases. However, their regulatory mechanisms and how they are connected to cargo proteins are still poorly understood. Accumulating data indicate that G protein-coupled receptors (GPCRs) directly associate with Rab GTPases and that these interactions dictate receptor trafficking. Yet, it remained unclear whether the receptors could regulate the targeting and activity of Rab GTPases in various cell compartments. It is only in recent years that experimental studies showed that GPCR signaling and interaction with Rab-associated regulatory proteins modulate the localization and activity of Rab GTPases. This research is revealing novel regulatory mechanisms of these small GTPases and should contribute to the progress in effective drug development. Recently published in the Journal of Cell Science, Lachance et al. present a novel role for ubiquitylation of Rab11a by a β2AR/HACE1 complex in regulating Rab11a activity and β2AR trafficking.
authors.affiliation: Service de Rhumatologie; Département de Médecine; Faculté de Médecine et des Sciences de la Santé; and the Institut de Pharmacologie de Sherbrooke; Université de Sherbrooke; and the Centre de Recherche du Centre Hospitalier de l'Université de Sherbrooke, Sherbrooke, QC Canada.
authors.forename: Véronik
authors.initials: V
authors.lastname: Lachance
authors.affiliation: Department of Pharmaceutical Sciences; Leslie Dan Faculty of Pharmacy; and the Department of Biochemistry; Faculty of Medicine; University of Toronto; Toronto, ON Canada.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Angers
authors.affiliation: Service de Rhumatologie; Département de Médecine; Faculté de Médecine et des Sciences de la Santé; and the Institut de Pharmacologie de Sherbrooke; Université de Sherbrooke; and the Centre de Recherche du Centre Hospitalier de l'Université de Sherbrooke, Sherbrooke, QC Canada.
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Parent
mesh_terms: D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D006801:Humans; D017368:Protein Prenylation; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics* / Q000378:metabolism*; D044767:Ubiquitin-Protein Ligases / Q000235:genetics*; D020691:rab GTP-Binding Proteins / Q000235:genetics*
chemical_list: D018343:Receptors, Adrenergic, beta-2; D044767:Ubiquitin-Protein Ligases; D019883:Alkyl and Aryl Transferases; D020691:rab GTP-Binding Proteins
keywords: G Protein-Coupled Receptors (GPCRs); HACE1; Rab GTPases; Rab11a; ubiquitylation; vesicular trafficking; β2AR