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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Main Authors: Sabine Schürmann, Georg Steffes, Dominique Manikowski, Philipp Kastl, Ursula Malkus, Shyam Bandari, Stefanie Ohlig, Corinna Ortmann, Rocio Rebollido-Rios, Mandy Otto, Harald Nüsse, Daniel Hoffmann, Christian Klämbt, Milos Galic, Jürgen Klingauf, Kay Grobe
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2018-03-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/33033
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spelling doaj-6a0f74376f5b4faab692c9a25021d50d2021-05-05T15:43:06ZengeLife Sciences Publications LtdeLife2050-084X2018-03-01710.7554/eLife.33033Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wingSabine Schürmann0Georg Steffes1Dominique Manikowski2Philipp Kastl3Ursula Malkus4Shyam Bandari5Stefanie Ohlig6Corinna Ortmann7Rocio Rebollido-Rios8Mandy Otto9Harald Nüsse10Daniel Hoffmann11https://orcid.org/0000-0003-2973-7869Christian Klämbt12Milos Galic13Jürgen Klingauf14Kay Grobe15https://orcid.org/0000-0002-8385-5877Institute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyCenter for Medical Biotechnology, University of Duisburg-Essen, Essen, Germany; Institute of Neurobiology, University of Münster, Münster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyInstitute of Medical Physics and Biophysics, University of Münster, Münster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyCenter for Medical Biotechnology, University of Duisburg-Essen, Essen, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyInstitute of Medical Physics and Biophysics, University of Münster, Münster, GermanyCenter for Medical Biotechnology, University of Duisburg-Essen, Essen, GermanyInstitute of Neurobiology, University of Münster, Münster, GermanyInstitute of Medical Physics and Biophysics, University of Münster, Münster, GermanyInstitute of Medical Physics and Biophysics, University of Münster, Münster, GermanyInstitute of Physiological Chemistry and Pathobiochemistry, University of Münster, Münster, Germany; Cells-in-Motion Cluster of Excellence (EXC1003-CiM), University of Münster, Münster, GermanyCell 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.https://elifesciences.org/articles/33033hedgehogmorphogenpatterningwingproteolysis
collection DOAJ
language English
format Article
sources DOAJ
author Sabine Schürmann
Georg Steffes
Dominique Manikowski
Philipp Kastl
Ursula Malkus
Shyam Bandari
Stefanie Ohlig
Corinna Ortmann
Rocio Rebollido-Rios
Mandy Otto
Harald Nüsse
Daniel Hoffmann
Christian Klämbt
Milos Galic
Jürgen Klingauf
Kay Grobe
spellingShingle Sabine Schürmann
Georg Steffes
Dominique Manikowski
Philipp Kastl
Ursula Malkus
Shyam Bandari
Stefanie Ohlig
Corinna Ortmann
Rocio Rebollido-Rios
Mandy Otto
Harald Nüsse
Daniel Hoffmann
Christian Klämbt
Milos Galic
Jürgen Klingauf
Kay Grobe
Proteolytic processing of palmitoylated Hedgehog peptides specifies the 3-4 intervein region of the Drosophila wing
eLife
hedgehog
morphogen
patterning
wing
proteolysis
author_facet Sabine Schürmann
Georg Steffes
Dominique Manikowski
Philipp Kastl
Ursula Malkus
Shyam Bandari
Stefanie Ohlig
Corinna Ortmann
Rocio Rebollido-Rios
Mandy Otto
Harald Nüsse
Daniel Hoffmann
Christian Klämbt
Milos Galic
Jürgen Klingauf
Kay Grobe
author_sort Sabine Schürmann
title 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_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_sort proteolytic processing of palmitoylated hedgehog peptides specifies the 3-4 intervein region of the drosophila wing
publisher eLife Sciences Publications Ltd
series eLife
issn 2050-084X
publishDate 2018-03-01
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.
topic hedgehog
morphogen
patterning
wing
proteolysis
url https://elifesciences.org/articles/33033
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