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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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 |
work_keys_str_mv |
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