Functional characterization of a C-terminal splice variant of the human melanocortin 1 receptor.

Martínez-Vicente, Idoya; Abrisqueta, Marta; García-Borrón Martínez, José Carlos; Herraiz Serrano, Cecilia María; Jiménez-Cervantes Frigols, Celia; Olivares Sánchez, María Concepción

Publication:
Functional characterization of a C-terminal splice variant of the human melanocortin 1 receptor.

dc.contributor.author	Martínez-Vicente, Idoya
dc.contributor.author	Abrisqueta, Marta
dc.contributor.author	García-Borrón Martínez, José Carlos
dc.contributor.author	Herraiz Serrano, Cecilia María
dc.contributor.author	Jiménez-Cervantes Frigols, Celia
dc.contributor.author	Olivares Sánchez, María Concepción
dc.contributor.department	Bioquímica y Biología Molecular B e Inmunología
dc.date.accessioned	2025-01-21T07:50:09Z
dc.date.available	2025-01-21T07:50:09Z
dc.date.issued	2020-05-31
dc.description	© 2020 John Wiley & Sons A/S. This document is the 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
dc.description.abstract	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.
dc.format	application/pdf	es
dc.format.extent	6
dc.identifier.citation	Experimental Dermatology. 2020 29:610–615
dc.identifier.doi	https://doi.org/10.1111/exd.14118
dc.identifier.issn	Print: 0906-6705
dc.identifier.issn	Electronic: 1600-0625
dc.identifier.uri	http://hdl.handle.net/10201/148884
dc.language	eng	es
dc.publisher	Wiley
dc.relation	Fundación Seneca, CARM, Grant/Award Number: 19875/GERM/15; Ministerio de Economía y Competitividad, Grant/Award Number: SAF2018_RTI2018-094929-B-I00	es
dc.relation.publisherversion	https://onlinelibrary.wiley.com/doi/10.1111/exd.14118
dc.rights.accessRights	info:eu-repo/semantics/restrictedAccess
dc.subject	Desensitization
dc.subject	Functional coupling
dc.subject	Melanocortin 1 receptor, Melanoma
dc.subject	Splice variants
dc.title	Functional characterization of a C-terminal splice variant of the human melanocortin 1 receptor.	es
dc.type	info:eu-repo/semantics/article	es
dspace.entity.type	Publication	es
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