C-Terminal Peptide Modifications Reveal Direct and Indirect Roles of Hedgehog Morphogen Cholesteroylation.

Drosophila Sonic hedgehog hedgehog morphogen proteolysis signaling

Journal

Frontiers in cell and developmental biology
ISSN: 2296-634X
Titre abrégé: Front Cell Dev Biol
Pays: Switzerland
ID NLM: 101630250

Informations de publication

Date de publication:
2020
Historique:
received: 09 10 2020
accepted: 03 12 2020
entrez: 29 1 2021
pubmed: 30 1 2021
medline: 30 1 2021
Statut: epublish

Résumé

Hedgehog (Hh) morphogens are involved in embryonic development and stem cell biology and, if misregulated, can contribute to cancer. One important post-translational modification with profound impact on Hh biofunction is its C-terminal cholesteroylation during biosynthesis. The current hypothesis is that the cholesterol moiety is a decisive factor in Hh association with the outer plasma membrane leaflet of producing cells, cell-surface Hh multimerization, and its transport and signaling. Yet, it is not decided whether the cholesterol moiety is directly involved in all of these processes, because their functional interdependency raises the alternative possibility that the cholesterol initiates early processes directly and that these processes can then steer later stages of Hh signaling independent of the lipid. We generated variants of the C-terminal Hh peptide and observed that these cholesteroylated peptides variably impaired several post-translational processes in producing cells and Hh biofunction in

Identifiants

pubmed: 33511123
doi: 10.3389/fcell.2020.615698
pmc: PMC7835520
doi:

Types de publication

Journal Article

Langues

eng

Pagination

615698

Informations de copyright

Copyright © 2021 Manikowski, Kastl, Schürmann, Ehring, Steffes, Jakobs and Grobe.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Dominique Manikowski (D)

Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.

Philipp Kastl (P)

Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.

Sabine Schürmann (S)

Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.

Kristina Ehring (K)

Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.

Georg Steffes (G)

Institute of Neuro- and Behavioral Biology, University of Münster, Münster, Germany.

Petra Jakobs (P)

Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.

Kay Grobe (K)

Institute of Physiological Chemistry and Pathobiochemistry and the Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, Germany.

Classifications MeSH