Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing

Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producin...

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Autores principales: Schürmann, Sabine, Steffes, Georg, Manikowski, Dominique, Kastl, Philipp, Malkus, Ursula, Bandari, Shyam, Ohlig, Stefanie, Ortmann, Corinna, Rebollido-Rios, Rocio, Otto, Mandy, Nüsse, Harald, Hoffmann, Daniel, Klämbt, Christian, Galic, Milos, Klingauf, Jürgen, Grobe, Kay
Formato: Online Artículo Texto
Lenguaje:English
Publicado: eLife Sciences Publications, Ltd 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844694/
https://www.ncbi.nlm.nih.gov/pubmed/29522397
http://dx.doi.org/10.7554/eLife.33033
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author Schürmann, Sabine
Steffes, Georg
Manikowski, Dominique
Kastl, Philipp
Malkus, Ursula
Bandari, Shyam
Ohlig, Stefanie
Ortmann, Corinna
Rebollido-Rios, Rocio
Otto, Mandy
Nüsse, Harald
Hoffmann, Daniel
Klämbt, Christian
Galic, Milos
Klingauf, Jürgen
Grobe, Kay
author_facet Schürmann, Sabine
Steffes, Georg
Manikowski, Dominique
Kastl, Philipp
Malkus, Ursula
Bandari, Shyam
Ohlig, Stefanie
Ortmann, Corinna
Rebollido-Rios, Rocio
Otto, Mandy
Nüsse, Harald
Hoffmann, Daniel
Klämbt, Christian
Galic, Milos
Klingauf, Jürgen
Grobe, Kay
author_sort Schürmann, Sabine
collection PubMed
description Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions.
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spelling pubmed-58446942018-03-12 Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing Schürmann, Sabine Steffes, Georg Manikowski, Dominique Kastl, Philipp Malkus, Ursula Bandari, Shyam Ohlig, Stefanie Ortmann, Corinna Rebollido-Rios, Rocio Otto, Mandy Nüsse, Harald Hoffmann, Daniel Klämbt, Christian Galic, Milos Klingauf, Jürgen Grobe, Kay eLife Cell Biology Cell fate determination during development often requires morphogen transport from producing to distant responding cells. Hedgehog (Hh) morphogens present a challenge to this concept, as all Hhs are synthesized as terminally lipidated molecules that form insoluble clusters at the surface of producing cells. While several proposed Hh transport modes tie directly into these unusual properties, the crucial step of Hh relay from producing cells to receptors on remote responding cells remains unresolved. Using wing development in Drosophila melanogaster as a model, we show that Hh relay and direct patterning of the 3–4 intervein region strictly depend on proteolytic removal of lipidated N-terminal membrane anchors. Site-directed modification of the N-terminal Hh processing site selectively eliminated the entire 3–4 intervein region, and additional targeted removal of N-palmitate restored its formation. Hence, palmitoylated membrane anchors restrict morphogen spread until site-specific processing switches membrane-bound Hh into bioactive forms with specific patterning functions. eLife Sciences Publications, Ltd 2018-03-09 /pmc/articles/PMC5844694/ /pubmed/29522397 http://dx.doi.org/10.7554/eLife.33033 Text en © 2018, Schürmann et al http://creativecommons.org/licenses/by/4.0/ http://creativecommons.org/licenses/by/4.0/This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use and redistribution provided that the original author and source are credited.
spellingShingle Cell Biology
Schürmann, Sabine
Steffes, Georg
Manikowski, Dominique
Kastl, Philipp
Malkus, Ursula
Bandari, Shyam
Ohlig, Stefanie
Ortmann, Corinna
Rebollido-Rios, Rocio
Otto, Mandy
Nüsse, Harald
Hoffmann, Daniel
Klämbt, Christian
Galic, Milos
Klingauf, Jürgen
Grobe, Kay
Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
title Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
title_full Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
title_fullStr Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
title_full_unstemmed Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
title_short Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
title_sort proteolytic processing of palmitoylated hedgehog peptides specifies the 3-4 intervein region of the drosophila wing
topic Cell Biology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5844694/
https://www.ncbi.nlm.nih.gov/pubmed/29522397
http://dx.doi.org/10.7554/eLife.33033
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