Por favor, use este identificador para citar o enlazar este ítem: https://doi.org/10.1111/exd.14118

Título: Functional characterization of a C-terminal splice variant of the human melanocortin 1 receptor.
Fecha de publicación: 31-may-2020
Editorial: Wiley
Cita bibliográfica: Experimental Dermatology. 2020;29:610–615
ISSN: Print: 0906-6705
Electronic: 1600-0625
Palabras clave: Desensitization
Functional coupling
Melanocortin 1 receptor, Melanoma
Splice variants
Resumen: The melanocortin 1 receptor (MC1R) is a major determinant of skin pigmentation and sensitivity to ultraviolet radiation. When stimulated by its natural agonists, it promotes the switch from synthesis of poorly photoprotective and lightly colored pheomelanins to production of photoprotective and darker eumelanins. In addition to an unusually high number of single nucleotide polymorphisms, the MC1R is expressed as 3 protein-coding splice variants. Two transcripts display different 5’ untranslated sequences but yield the same open reading frame corresponding to the canonical 317 aminoacids protein (termed MC1R). An alternative transcript named MC1R-203 encodes for a 382 amino acids protein of poorly characterized functional properties containing an additional 65 aminoacids C-terminal extension. Given the known roles of the MC1R C-terminal extension in forward trafficking, coupling to intracellular effectors and desensitization, the different structure of this domain in MC1R and MC1R-203 may lead to significant functional alteration(s). We have assessed the functional properties of MC1R-203, as compared with the canonical MC1R form. We show that unstimulated HBL human melanoma cells express the MC1R-203 spliceoform, although at much lower levels than canonical MC1R. When expressed in heterologous HEK293 cells, the presence of the 65 aminoacid-long cytosolic extension immediately after Cys316 in MC1R-203 did not impair the intracellular stability of the protein, but it interfered with functional coupling to the cAMP cascade and with the ubiquitylation of ARRB2 associated with MC1R desensitization. Conversely, MC1R-203 retained full capacity to activate ERK1/2 signaling. Accordingly, MC1R203 displays biased signaling when expressed in HEK293 cells.
Autor/es principal/es: Martínez-Vicente, Idoya
Abrisqueta, Marta
Herraiz Serrano, Cecilia María
Jiménez-Cervantes, Celia
García-Borrón, José Carlos
Olivares, Conchi
Versión del editor: https://onlinelibrary.wiley.com/doi/10.1111/exd.14118
URI: http://hdl.handle.net/10201/148884
DOI: https://doi.org/10.1111/exd.14118
Tipo de documento: info:eu-repo/semantics/article
Número páginas / Extensión: 6
Derechos: info:eu-repo/semantics/embargoedAccess
Descripción: © 2020 John Wiley & Sons A/S. This document is the Submitted Published version of a Published Work that appeared in final form in Experimental Dermatology. To access the final edited and published work see https://doi.org/10.1111/exd.14118
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