title: Rab26 modulates the cell surface transport of α2-adrenergic receptors from the Golgi.
abstract: The molecular mechanisms underlying the transport from the Golgi to the cell surface of G protein-coupled receptors remain poorly elucidated. Here we determined the role of Rab26, a Ras-like small GTPase involved in vesicle-mediated secretion, in the cell surface export of α(2)-adrenergic receptors. We found that transient expression of Rab26 mutants and siRNA-mediated depletion of Rab26 significantly attenuated the cell surface numbers of α(2A)-AR and α(2B)-AR, as well as ERK1/2 activation by α(2B)-AR. Furthermore, the receptors were extensively arrested in the Golgi by Rab26 mutants and siRNA. Moreover, Rab26 directly and activation-dependently interacted with α(2B)-AR, specifically the third intracellular loop. These data demonstrate that the small GTPase Rab26 regulates the Golgi to cell surface traffic of α(2)-adrenergic receptors, likely through a physical interaction. These data also provide the first evidence implicating an important function of Rab26 in coordinating plasma membrane protein transport.
authors.affiliation: Department of Pharmacology and Toxicology, Georgia Health Sciences University, Augusta, Georgia 30912, USA.
authors.forename: Chunman
authors.initials: C
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Fan
authors.forename: Tien-Hung
authors.initials: TH
authors.lastname: Lan
authors.forename: Nevin A
authors.initials: NA
authors.lastname: Lambert
authors.forename: Guangyu
authors.initials: G
authors.lastname: Wu
mesh_terms: D015415:Biomarkers / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism*; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D055785:Gene Knockdown Techniques; D006056:Golgi Apparatus / Q000378:metabolism*; D000077614:Golgi Matrix Proteins; D057809:HEK293 Cells; D006801:Humans; D061986:MCF-7 Cells; D008565:Membrane Proteins / Q000378:metabolism; D050505:Mutant Proteins / Q000378:metabolism; D011485:Protein Binding; D017433:Protein Structure, Secondary; D021381:Protein Transport; D034741:RNA, Small Interfering / Q000378:metabolism; D018341:Receptors, Adrenergic, alpha-2 / Q000737:chemistry / Q000378:metabolism*; D020691:rab GTP-Binding Proteins / Q000737:chemistry / Q000378:metabolism*
chemical_list: C547768:ADRA2A protein, human; D015415:Biomarkers; D000077614:Golgi Matrix Proteins; D008565:Membrane Proteins; D050505:Mutant Proteins; D034741:RNA, Small Interfering; D018341:Receptors, Adrenergic, alpha-2; C087574:macrogolgin; D048049:Extracellular Signal-Regulated MAP Kinases; C578286:Rab26 protein, human; D020691:rab GTP-Binding Proteins