» Articles » PMID: 27547735

Regulation of Hedgehog Signalling Inside and Outside the Cell

Overview
Journal J Dev Biol
Specialty Biology
Date 2016 Aug 23
PMID 27547735
Citations 40
Authors
Affiliations
Soon will be listed here.
Abstract

The hedgehog (Hh) signalling pathway is conserved throughout metazoans and plays an important regulatory role in both embryonic development and adult homeostasis. Many levels of regulation exist that control the release, reception, and interpretation of the hedgehog signal. The fatty nature of the Shh ligand means that it tends to associate tightly with the cell membrane, and yet it is known to act as a morphogen that diffuses to elicit pattern formation. Heparan sulfate proteoglycans (HSPGs) play a major role in the regulation of Hh distribution outside the cell. Inside the cell, the primary cilium provides an important hub for processing the Hh signal in vertebrates. This review will summarise the current understanding of how the Hh pathway is regulated from ligand production, release, and diffusion, through to signal reception and intracellular transduction.

Citing Articles

Identification of small molecule antagonists of sonic hedgehog/heparin binding with activity in hedgehog functional assays.

Lamson D, Tarpley M, Addo K, Ji X, Abu Rabe D, Ehe B Biochim Biophys Acta Gen Subj. 2024; 1868(11):130692.

PMID: 39151833 PMC: 11486593. DOI: 10.1016/j.bbagen.2024.130692.


A Pilot Immunohistochemical Study Identifies Hedgehog Pathway Expression in Sinonasal Adenocarcinoma.

Leovic M, Jakovcevic A, Mumlek I, Zagorac I, Sabol M, Leovic D Int J Mol Sci. 2024; 25(9).

PMID: 38731849 PMC: 11083810. DOI: 10.3390/ijms25094630.


Hedgehog costimulation during ischemia-reperfusion injury potentiates cytokine and homing responses of CD4 T cells.

Wang S, Song G, Barkestani M, Tobiasova Z, Wang Q, Jiang Q Front Immunol. 2023; 14:1248027.

PMID: 37915586 PMC: 10616247. DOI: 10.3389/fimmu.2023.1248027.


Hedgehog signaling in tissue homeostasis, cancers, and targeted therapies.

Jing J, Wu Z, Wang J, Luo G, Lin H, Fan Y Signal Transduct Target Ther. 2023; 8(1):315.

PMID: 37596267 PMC: 10439210. DOI: 10.1038/s41392-023-01559-5.


Hedgehog-induced ZFYVE21 promotes chronic vascular inflammation by activating NLRP3 inflammasomes in T cells.

Jiang B, Wang S, Song G, Jiang Q, Fan M, Fang C Sci Signal. 2023; 16(777):eabo3406.

PMID: 36943921 PMC: 10061549. DOI: 10.1126/scisignal.abo3406.


References
1.
Goodrich L, Milenkovic L, Higgins K, Scott M . Altered neural cell fates and medulloblastoma in mouse patched mutants. Science. 1997; 277(5329):1109-13. DOI: 10.1126/science.277.5329.1109. View

2.
Ruiz i Altaba A . Combinatorial Gli gene function in floor plate and neuronal inductions by Sonic hedgehog. Development. 1998; 125(12):2203-12. DOI: 10.1242/dev.125.12.2203. View

3.
Kovacs J, Whalen E, Liu R, Xiao K, Kim J, Chen M . Beta-arrestin-mediated localization of smoothened to the primary cilium. Science. 2008; 320(5884):1777-81. PMC: 2587210. DOI: 10.1126/science.1157983. View

4.
Barzi M, Berenguer J, Menendez A, Alvarez-Rodriguez R, Pons S . Sonic-hedgehog-mediated proliferation requires the localization of PKA to the cilium base. J Cell Sci. 2009; 123(Pt 1):62-9. DOI: 10.1242/jcs.060020. View

5.
Lewis P, Dunn M, McMahon J, Logan M, Martin J, St-Jacques B . Cholesterol modification of sonic hedgehog is required for long-range signaling activity and effective modulation of signaling by Ptc1. Cell. 2001; 105(5):599-612. DOI: 10.1016/s0092-8674(01)00369-5. View