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

Abstract

The melanocortin 1 receptor (MC1R) is a major determinant of skin pigmentation and sensitivity to ultraviolet radiation (UVR). [1] When stimulated by its natural agonists, the melanocortin peptides αMSH and ACTH, it promotes the switch from synthesis of poorly photoprotective and lightly coloured pheomelanins to production of photoprotective and darker eumelanins. Several common variants of the

Behind the Scene: Exploiting MC1R in Skin Cancer Risk and Prevention

“…The MC1R gene may exhibit splice variants, giving rise to two forms of intergenic splicing, yielding MC1R-TUBB3 (β-tubulin III) chimera and at least two forms of alternative splicing [ 13 , 14 ]. In all cases, the proteins encoded by the non-canonical mRNAs preserve the general architecture of GPCRs and differ from canonical MC1R for a longer C-terminal extension [ 14 , 15 ].…”

Towards a renaissance of dermatoendocrinology: Selected current frontiers

“…[27,28] Other examples include unexpected twists of research on melanocortin peptides, its derivatives and receptors. [29,30] For instance, a C-terminal splice variant of the human melanocortin 1 receptor, a well-established key regulator of skin pigmentation, has recently been highlighted. [29] However, the expression of the splice variant may change the signalling properties of the co-expressed non-splicoform.…”

“…[29,30] For instance, a C-terminal splice variant of the human melanocortin 1 receptor, a well-established key regulator of skin pigmentation, has recently been highlighted. [29] However, the expression of the splice variant may change the signalling properties of the co-expressed non-splicoform. This unexpected finding could kick-off subsequent research on other cutaneous cell types expressing the above receptor.…”

The α‐melanocyte‐stimulating hormone/melanocortin‐1 receptor interaction: A driver of pleiotropic effects beyond pigmentation

“…MC1R gene is located on chromosome 16q24.3 and has 4 exons, giving rise to several intra‐ and intergenic splice variants. Two forms of intergenic splicing yielding MC1R‐TUBB3 chimerae and at least two forms of alternative splicing of the MC1R gene have been described (Dalziel et al., 2011; Herraiz et al., 2015; Martínez‐Vicente et al., 2020; Tan et al, 1999). In all cases, the proteins encoded by the non‐canonical mRNAs preserve the general architecture of GPCRs and differ from canonical MC1R by the presence of a longer cytosolic extension.…”

“…In all cases, the proteins encoded by the non‐canonical mRNAs preserve the general architecture of GPCRs and differ from canonical MC1R by the presence of a longer cytosolic extension. Since the regions of the MC1R molecule involved in ligand binding and functional coupling to G proteins are present in all these splicing products, their functional properties have been analyzed to determine the effect of the additional C‐terminal extension in MC1R splice variants compared with canonical MC1R (Herraiz et al., 2015; Martínez‐Vicente et al., 2020). All the non‐canonical proteins have been found to display reduced signaling to the cAMP pathway, although most of them are still able to activate the ERKs.…”