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...
Autores principales: | , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
eLife Sciences Publications, Ltd
2018
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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. |
format | Online Article Text |
id | pubmed-5844694 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | eLife Sciences Publications, Ltd |
record_format | MEDLINE/PubMed |
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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