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Constitutive traffic of melanocortin-4 receptor in Neuro2A cells and immortalized hypothalamic neurons.
Mohammad, Sameer; Baldini, Giovanna; Granell, Susana; Narducci, Paola; Martelli, Alberto M; Baldini, Giulia.
Afiliação
  • Mohammad S; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
  • Baldini G; Dipartimento di Morfologia Umana Normale, via Manzoni 16, Universita' di Trieste, I-34138 Trieste, Italy, and the.
  • Granell S; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205.
  • Narducci P; Dipartimento di Morfologia Umana Normale, via Manzoni 16, Universita' di Trieste, I-34138 Trieste, Italy, and the.
  • Martelli AM; Dipartimento di Scienze Anatomiche Umane e Fisiopatologia dell'Apparato Locomotore, Sezione di Anatomia, Cell Signalling Laboratory, Universita' di Bologna, via Irnerio 48, I-40126 Bologna, Italy.
  • Baldini G; Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, Arkansas 72205. Electronic address: gbaldini@uams.edu.
J Biol Chem ; 282(7): 4963-4974, 2007 Feb 16.
Article em En | MEDLINE | ID: mdl-17166828
Melanocortin-4 receptor (MC4R) is a G protein-coupled receptor (GPCR) that binds alpha-melanocyte-stimulating hormone (alpha-MSH) and has a central role in the regulation of appetite and energy expenditure. Most GPCRs are endocytosed following binding to the agonist and receptor desensitization. Other GPCRs are internalized and recycled back to the plasma membrane constitutively, in the absence of the agonist. In unstimulated neuroblastoma cells and immortalized hypothalamic neurons, epitopetagged MC4R was localized both at the plasma membrane and in an intracellular compartment. These two pools of receptors were in dynamic equilibrium, with MC4R being rapidly internalized and exocytosed. In the absence of alpha-MSH, a fraction of cell surface MC4R localized together with transferrin receptor and to clathrin-coated pits. Constitutive MC4R internalization was impaired by expression of a dominant negative dynamin mutant. Thus, MC4R is internalized together with transferrin receptor by clathrin-dependent endocytosis. Cell exposure toalpha-MSH reduced the amount of MC4R at the plasma membrane by blocking recycling of a fraction of internalized receptor, rather than by increasing its rate of endocytosis. The data indicate that, in neuronal cells, MC4R recycles constitutively and that alpha-MSH modulates MC4R residency at the plasma membrane by acting at an intracellular sorting step.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Alfa-MSH / Receptor Tipo 4 de Melanocortina / Hipotálamo / Neurônios Idioma: En Revista: J Biol Chem Ano de publicação: 2007 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Alfa-MSH / Receptor Tipo 4 de Melanocortina / Hipotálamo / Neurônios Idioma: En Revista: J Biol Chem Ano de publicação: 2007 Tipo de documento: Article