Structural determinants regulating cell surface targeting of melanocortin receptors

    1. A M Gouveia1,2,4
    1. 1Department of Experimental Biology, Faculty of Medicine, University of Porto, Alameda Prof. Hernâni Monteiro, 4200-319 Porto, Portugal
      2Instituto de Biologia Molecular e Celular (IBMC), University of Porto, Porto, Portugal
      3IPATIMUP, Institute of Molecular Pathology and Immunology
      4Faculty of Nutrition and Food Sciences, University of Porto, Porto, Portugal
    1. Correspondence should be addressed to A M Gouveia; Email: agouveia{at}


    Melanocortin receptors (MCRs) belong to the G-protein-coupled receptor family of transmembrane proteins. They recognize specific ligands named melanocortins that are mainly produced in the pituitary and hypothalamus. Newly synthesized MCRs at the endoplasmic reticulum are subjected to quality control mechanisms that screen for the correct structure, folding or processing, essential for their proper cell surface expression. Some motifs, located at the N- or C-terminus or even on transmembrane and in loop regions, have been implicated in these biological processes. This article reviews these specific domains and the role of accessory proteins and post-translation modifications in MCRs' targeting to cell surface. Additionally, promising approaches involving pharmacological stabilization of misfolded and misrouted mutant MCRs, which improve their forward transport, are reported. Understanding the MCRs' structural determinants fundamental for their proper cell surface integration is essential for correcting abnormalities found in some diseases.

    • Revision received 25 July 2013
    • Accepted 31 July 2013
    • Made available online as an Accepted Preprint 1 August 2013
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