Immunomodulatory potential of primary cilia in the skin DOI Creative Commons

Jingwei Sun,

Huimin Yuan,

Yanru Yu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 29, 2024

Primary cilia (PC) are essential signaling hubs for proper epithelial formation and the maintenance of skin homeostasis. Found on most cells in human body, including cells, PC facilitate signal transduction that allows ciliated to interact with immune system via multiple pathways, helping maintain can be altered by various microenvironmental stimuli develop corresponding regulatory functions. Both ciliary pathways have been shown involved processes lesions. However, mechanisms which regulate cellular functions homeostasis tissues highly complex, our understanding them remains limited. In this paper, we discuss key skin, a focus their immunomodulatory We compiled evidence from disease models help explore potential effects molecular mechanisms.

Language: Английский

Receptor Allostery Promotes Context-Specific Sonic Hedgehog Signaling During Embryonic Development DOI Creative Commons
Shariq S. Ansari, Miriam E. Dillard, Mohamed Ghonim

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Abstract Sonic Hedgehog (SHH) signaling functions in temporal- and context-dependent manners to pattern diverse tissues during embryogenesis. The signal transducer Smoothened (SMO) is activated by sterols, oxysterols, arachidonic acid (AA) through binding pockets its extracellular cysteine-rich domain (CRD) 7-transmembrane (7TM) bundle. In vitro analyses suggest SMO allosterically enhanced combinatorial ligand these but vivo evidence of allostery lacking. Herein, we map an AA pocket at the top 7TM bundle show that disruption attenuates SHH sterol-stimulated induction. A knockin mouse model compromised reveals homozygous mutant mice are cyanotic, exhibit high perinatal lethality, congenital heart disease. Surviving mutants demonstrate pulmonary maldevelopment fail thrive. Neurodevelopment unaltered mice, suggesting allosteric regulation allows for precise tuning pathway activity cardiopulmonary development.

Language: Английский

Citations

0
BBSome-deficient cells activate intraciliary CDC42 to trigger actin-dependent ciliary ectocytosis DOI Creative Commons
Avishek Prasai, Olha Ivashchenko, Kristyna Maskova

et al.

EMBO Reports, Journal Year: 2024, Volume and Issue: unknown

Published: Nov. 25, 2024

Language: Английский

Citations

1
Melanocortin 1 receptor mediates melanin production by interacting with the BBSome in primary cilia DOI Creative Commons
Xiaoyu Tian,

Hanyu Wang,

Song Liu

et al.

PLoS Biology, Journal Year: 2024, Volume and Issue: 22(12), P. e3002940 - e3002940

Published: Dec. 2, 2024

Production of melanin pigments is a protective mechanism the skin against ultraviolet (UV)-induced damage and carcinogenesis. However, molecular basis for melanogenesis still poorly understood. Herein, we demonstrate critical interplay between primary cilium melanocortin 1 receptor (MC1R) signaling. Our data show that UV α-melanocyte-stimulating hormone (α-MSH) trigger formation in human melanocytes melanoma cells. Deficiency MC1R or presence its red hair color (RHC) variations significantly attenuates UV/α-MSH-induced ciliogenesis. Further investigation reveals enters upon UV/α-MSH stimulation, which facilitated by interaction with BBSome palmitoylation MC1R. interacts through second third intercellular loops, contain common RHC variant alleles (R151C R160W). These variants exhibit attenuated ciliary localization, enforced localization these elevates melanogenesis. Ciliary triggers sustained cAMP signaling selectively stimulates Sox9, appears to up-regulate melanogenesis-related genes as transcriptional cofactor MITF. findings reveal previously unrecognized nexus cilia suggest an important variant-related pigmentary defects.

Language: Английский

Citations

1
Immunomodulatory potential of primary cilia in the skin DOI Creative Commons

Jingwei Sun,

Huimin Yuan,

Yanru Yu

et al.

Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 15

Published: Nov. 29, 2024

Primary cilia (PC) are essential signaling hubs for proper epithelial formation and the maintenance of skin homeostasis. Found on most cells in human body, including cells, PC facilitate signal transduction that allows ciliated to interact with immune system via multiple pathways, helping maintain can be altered by various microenvironmental stimuli develop corresponding regulatory functions. Both ciliary pathways have been shown involved processes lesions. However, mechanisms which regulate cellular functions homeostasis tissues highly complex, our understanding them remains limited. In this paper, we discuss key skin, a focus their immunomodulatory We compiled evidence from disease models help explore potential effects molecular mechanisms.

Language: Английский

Citations

0