Hedgehog lipids: Promotors of alternative morphogen release and signaling?: Conflicting findings on lipidated Hedgehog transport and signaling can be explained by alternative regulated mechanisms to release the morphogen.
cholesterol
dispatched1
hedgehog
morphogen
patched1
scube2
shedding
Journal
BioEssays : news and reviews in molecular, cellular and developmental biology
ISSN: 1521-1878
Titre abrégé: Bioessays
Pays: United States
ID NLM: 8510851
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
revised:
27
08
2021
received:
26
05
2021
accepted:
06
09
2021
pubmed:
7
10
2021
medline:
30
11
2021
entrez:
6
10
2021
Statut:
ppublish
Résumé
Two posttranslational lipid modifications present on all Hedgehog (Hh) morphogens-an N-terminal palmitate and a C-terminal cholesterol-are established and essential regulators of Hh biofunction. Yet, for several decades, the question of exactly how both lipids contribute to Hh signaling remained obscure. Recently, cryogenic electron microscopy revealed different modes by which one or both lipids may contribute directly to Hh binding and signaling to its receptor Patched1 (Ptc). Some of these modes demand that the established release factor Dispatched1 (Disp) extracts dual-lipidated Hh from the cell surface, and that another known upstream signaling modulator called Scube2 chaperones the dual-lipidated morphogen to Ptc. By mechanistically and biochemically aligning this concept with established in vivo and recent in vitro findings, this reflection identifies remaining questions in lipidated Hh transport and evaluates additional mechanisms of Disp- and Scube2-regulated release of a second bioactive Hh fraction that has one or both lipids removed.
Identifiants
pubmed: 34611914
doi: 10.1002/bies.202100133
doi:
Substances chimiques
Drosophila Proteins
0
Hedgehog Proteins
0
Cholesterol
97C5T2UQ7J
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2100133Informations de copyright
© 2021 Wiley Periodicals LLC.
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