» Articles » PMID: 32084300

Signaling in the Primary Cilium Through the Lens of the Hedgehog Pathway

Overview
Specialty Biology
Date 2020 Feb 22
PMID 32084300
Citations 39
Authors
Affiliations
Soon will be listed here.
Abstract

Cilia are microtubule-based, cell-surface projections whose machinery is evolutionarily conserved. In vertebrates, cilia are observed on almost every cell type and are either motile or immotile. Immotile sensory, or primary cilia, are responsive to extracellular ligands and signals. Cilia can be thought of as compartments, functionally distinct from the cell that provides an environment for signaling cascades. Hedgehog is a critical developmental signaling pathway which is functionally linked to primary cilia in vertebrates. The major components of the vertebrate Hedgehog signaling pathway dynamically localize to the ciliary compartment and ciliary membrane. Critically, G-protein coupled receptor (GPCR) Smoothened, the obligate transducer of the pathway, is enriched and activated in the cilium. While Smoothened is the most intensely studied ciliary receptor, many GPCRs localize within cilia. Understanding the link between Smoothened and cilia defines common features, and distinctions, of GPCR signaling within the primary cilium. This article is categorized under: Signaling Pathways > Global Signaling Mechanisms Signaling Pathways > Cell Fate Signaling.

Citing Articles

Tonic ubiquitination of the central body weight regulator melanocortin receptor 4 (MC4R) promotes its constitutive exit from cilia.

Ojeda-Naharros I, Das T, Castro R, Bazan J, Vaisse C, Nachury M PLoS Biol. 2025; 23(2):e3003025.

PMID: 39899600 PMC: 11825094. DOI: 10.1371/journal.pbio.3003025.


GPATCH11 variants cause mis-splicing and early-onset retinal dystrophy with neurological impairment.

Zanetti A, Dujardin G, Fares-Taie L, Amiel J, Roger J, Audo I Nat Commun. 2024; 15(1):10096.

PMID: 39572588 PMC: 11582697. DOI: 10.1038/s41467-024-54549-8.


GRK2 kinases in the primary cilium initiate SMOOTHENED-PKA signaling in the Hedgehog cascade.

Walker M, Zhang J, Steiner W, Ku P, Zhu J, Michaelson Z PLoS Biol. 2024; 22(8):e3002685.

PMID: 39138140 PMC: 11322411. DOI: 10.1371/journal.pbio.3002685.


The Immune Checkpoint Protein PD-L1 Regulates Ciliogenesis and Hedgehog Signaling.

Agborbesong E, Li X Cells. 2024; 13(12.

PMID: 38920633 PMC: 11201989. DOI: 10.3390/cells13121003.


Deciphering vesicle-assisted transport mechanisms in cytoplasm to cilium trafficking.

Tingey M, Ruba A, Jiang Z, Yang W Front Cell Neurosci. 2024; 18:1379976.

PMID: 38860265 PMC: 11163138. DOI: 10.3389/fncel.2024.1379976.


References
1.
Chen W, Ren X, Nelson C, Barak L, Chen J, Beachy P . Activity-dependent internalization of smoothened mediated by beta-arrestin 2 and GRK2. Science. 2004; 306(5705):2257-60. DOI: 10.1126/science.1104135. View

2.
Dorn K, Hughes C, Rohatgi R . A Smoothened-Evc2 complex transduces the Hedgehog signal at primary cilia. Dev Cell. 2012; 23(4):823-35. PMC: 3586260. DOI: 10.1016/j.devcel.2012.07.004. View

3.
Berbari N, Johnson A, Lewis J, Askwith C, Mykytyn K . Identification of ciliary localization sequences within the third intracellular loop of G protein-coupled receptors. Mol Biol Cell. 2008; 19(4):1540-7. PMC: 2291422. DOI: 10.1091/mbc.e07-09-0942. View

4.
Ma M, Tian X, Igarashi P, Pazour G, Somlo S . Loss of cilia suppresses cyst growth in genetic models of autosomal dominant polycystic kidney disease. Nat Genet. 2013; 45(9):1004-12. PMC: 3758452. DOI: 10.1038/ng.2715. View

5.
Blassberg R, MacRae J, Briscoe J, Jacob J . Reduced cholesterol levels impair Smoothened activation in Smith-Lemli-Opitz syndrome. Hum Mol Genet. 2015; 25(4):693-705. PMC: 4743690. DOI: 10.1093/hmg/ddv507. View