Metabolites in vertebrate Hedgehog signaling

Hanne Roberg-Larsen; Martin Frank Strand; Stefan Krauss; Steven Ray Wilson

doi:10.1016/j.bbrc.2014.01.087

Metabolites in vertebrate Hedgehog signaling

Biochem Biophys Res Commun. 2014 Apr 11;446(3):669-74. doi: 10.1016/j.bbrc.2014.01.087. Epub 2014 Jan 30.

Authors

Hanne Roberg-Larsen¹, Martin Frank Strand², Stefan Krauss³, Steven Ray Wilson⁴

Affiliations

¹ Department of Chemistry, University of Oslo, PO Box 1033, Blindern, NO-0315 Oslo, Norway.
² Unit for Cell Signaling, SFI-CAST Biomedical Innovation Center, Oslo University Hospital, Rikshospitalet, NO-0027 Oslo, Norway; Atlantis Medical College, Sandakerveien 116, 0402 Oslo, Norway.
³ Unit for Cell Signaling, SFI-CAST Biomedical Innovation Center, Oslo University Hospital, Rikshospitalet, NO-0027 Oslo, Norway.
⁴ Department of Chemistry, University of Oslo, PO Box 1033, Blindern, NO-0315 Oslo, Norway. Electronic address: stevenw@kjemi.uio.no.

PMID: 24486313
DOI: 10.1016/j.bbrc.2014.01.087

Abstract

The Hedgehog (HH) signaling pathway is critical in embryonic development, stem cell biology, tissue homeostasis, chemoattraction and synapse formation. Irregular HH signaling is associated with a number of disease conditions including congenital disorders and cancer. In particular, deregulation of HH signaling has been linked to skin, brain, lung, colon and pancreatic cancers. Key mediators of the HH signaling pathway are the 12-pass membrane protein Patched (PTC), the 7-pass membrane protein Smoothened (SMO) and the GLI transcription factors. PTC shares homology with the RND family of small-molecule transporters and it has been proposed that it interferes with SMO through metabolites. Although a conclusive picture is lacking, substantial efforts are made to identify and understand natural metabolites/sterols, including cholesterol, vitamin D3, oxysterols and glucocorticoides, that may be affected by, or influence the HH signaling cascade at the level of PTC and SMO. In this review we will elaborate the role of metabolites in HH signaling with a focus on oxysterols, and discuss advancements in modern analytical approaches in the field.

Keywords: Hedgehog; Metabolites; Oxysterols; Patched; Smoothened; Sterols.

Publication types

Review

MeSH terms

Animals
Chemistry Techniques, Analytical / methods*
Glucocorticoids / metabolism*
Hedgehog Proteins / metabolism*
Humans
Patched Receptors
Receptors, Cell Surface / metabolism
Receptors, G-Protein-Coupled / metabolism
Signal Transduction
Smoothened Receptor
Sterols / analysis*
Sterols / metabolism*

Substances

Glucocorticoids
Hedgehog Proteins
Patched Receptors
Receptors, Cell Surface
Receptors, G-Protein-Coupled
SMO protein, human
Smoothened Receptor
Sterols