Production of melanin pigments is a protective mechanism of the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, the molecular basis for melanogenesis is still poorly understood. Herein, we demonstrate a critical interplay between the primary cilium and the melanocortin 1 receptor (MC1R) signaling. Our data show that UV and α-melanocyte-stimulating hormone (α-MSH) trigger cilium formation in human melanocytes and melanoma cells. Deficiency of MC1R or the presence of its red hair color (RHC) variations significantly attenuates the UV/α-MSH-induced ciliogenesis. Further investigation reveals that MC1R enters the cilium upon UV/α-MSH stimulation, which is facilitated by the interaction of MC1R with the BBSome and the palmitoylation of MC1R. MC1R interacts with the BBSome through the second and third intercellular loops, which contain the common RHC variant alleles (R151C and R160W). These RHC variants of MC1R exhibit attenuated ciliary localization, and enforced ciliary localization of these variants elevates melanogenesis. Ciliary MC1R triggers a sustained cAMP signaling and selectively stimulates Sox9, which appears to up-regulate melanogenesis-related genes as the transcriptional cofactor for MITF. These findings reveal a previously unrecognized nexus between MC1R and cilia and suggest an important mechanism for RHC variant-related pigmentary defects.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11637432 | PMC |
| http://dx.doi.org/10.1371/journal.pbio.3002940 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Systematic proteome-wide Mendelian randomization to prioritize causal plasma proteins for skin cancers.
Commun Biol
December 2024
Department of Computational Diagnostic Radiology and Preventive Medicine, The University of Tokyo Hospital, Tokyo, Japan.
Skin cancer is one of the most common cancers worldwide. Some risk factors including sun exposure and MC1R variants are recognized; however, the identification of additional genetic factors is essential for the development of novel therapeutic strategies. Here, we conducted a proteome-wide Mendelian randomization (MR) using plasma protein quantitative trait loci (pQTLs) from a published study and the UK Biobank genome-wide association study (GWAS) of skin cancers.
View Article and Find Full Text PDFDeciphering genetic characteristics of South China and North China indigenous pigs through selection signatures.
BMC Genomics
December 2024
State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou, 510642, China.
Background: Indigenous pig breeds in China have accumulated significant genetic diversity due to regional selection pressures. Investigating the selection signatures of these populations helps to understand their adaptive evolution and contributes to genetic improvement programs.
Results: We collected whole-genome sequencing data from 133 individuals, including South China and North China indigenous pigs and Asian wild boars.
Genome-Wide Association Study of Birth Wool Length, Birth Weight, and Head Color in Chinese Tan Sheep Through Whole-Genome Re-Sequencing.
Animals (Basel)
December 2024
College of Animal Science and Technology, Ningxia University, Yinchuan 750021, China.
Article Synopsis
- The Chinese Tan sheep breed, primarily raised in northwestern China, is valued for its lambskin and shiny white curly wool, with a focus on traits like wool length, birth weight, and head coat color in a study of 256 individuals.
- Whole genome sequencing yielded over 23 million high-quality SNPs, leading to the identification of 208 significant SNPs related to wool length, 1056 linked to birth weight (mostly on chromosome 2), and 1424 for head coat color (predominantly on chromosome 14).
- Further testing of head coat color-related SNPs confirmed five mutation sites on chromosome 14 and suggested that heterozygous genotypes may be responsible for the black-headed coat color in
Changes in Skin Cancer-Related Behaviors, Distress, and Beliefs in Response to Receipt of Low- to Moderate-Penetrance Genetic Test Results for Skin Cancer Risk.
Cancers (Basel)
November 2024
Department of Cancer Epidemiology, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33162, USA.
Little is known about the impact of low- to moderate-penetrance genetic testing for skin cancer, which is a promising approach to skin cancer prevention. To address this deficit, we conducted an analysis comparing changes in skin cancer-related behaviors, distress, and beliefs measured at a baseline and twice after the receipt of skin cancer precision prevention materials containing risk feedback (higher or average risk) among 568 non-Hispanic White (NHW) and 463 Hispanic participants. Regression analyses identified decreased average weekend hours in the sun (β = -0.
View Article and Find Full Text PDFAmbient ultraviolet-B exposure brings quantum changes in phenotypic and molecular signatures of the embryo of a high-altitude fish, Tor putitora.
Environ Sci Pollut Res Int
December 2024
ICAR-Directorate of Coldwater Fisheries Research, Anusandhan Bhawan, Bhimtal, 263136, Uttarakhand, India.
Effects of environmentally relevant ultraviolet B (UVB) light on the embryonic development of a high-altitude dwelling endangered fish, Tor putitora (golden mahseer), were investigated for the first time. For that, three sets of embryos (in triplicates) were exposed to various ambient UVB light doses (1, 2 and 3 W/m, corresponding to 3.6, 7.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!