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Lipids and Hedgehogs
Author(s) -
Salic Adrian,
Wierbowski Bradley,
Petrov Kostadin
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.00180
Subject(s) - morphogen , sonic hedgehog , microbiology and biotechnology , hedgehog signaling pathway , endoplasmic reticulum , embryonic stem cell , hedgehog , cell , biology , patched , chemistry , signal transduction , biochemistry , gene
The Hedgehog cell‐cell signaling pathway governs critical processes in the embryonic development of most animals, in adult stem cell maintenance, and in cancer. The pathway is activated by the secreted Hedgehog morphogen, such as the prototypical vertebrate homologue, Sonic hedgehog (SHH). SHH is generated in the endoplasmic reticulum of signal‐producing cells, as a hydrophobic protein uniquely modified with palmitate at the N‐terminus and with cholesterol at the C‐terminus. These lipid modifications, which are critical for SHH function, render SHH strongly attached to the plasma membrane; yet the SHH morphogen must travel through the extracellular space, to reach responding cells located far away. I will present our recent work aimed at elucidating the biochemical mechanisms that allow the lipidated SHH morphogen to be released in diffusible form from producing cells, and then be delivered to its receptor, the tumor suppressor membrane protein Patched1, on the surface of responding cells. Support or Funding Information NIH/NIGMS R01 GM122920