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Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion

Hedgehog (Hh) is a secreted morphogen involved in both short- and long-range signaling necessary for tissue patterning during development. It is unclear how this dually lipidated protein is transported over a long range in the aqueous milieu of interstitial spaces. We previously showed that the long...

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Autores principales: Parchure, Anup, Vyas, Neha, Ferguson, Charles, Parton, Robert G., Mayor, Satyajit
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The American Society for Cell Biology 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678025/
https://www.ncbi.nlm.nih.gov/pubmed/26490120
http://dx.doi.org/10.1091/mbc.E15-09-0671
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author Parchure, Anup
Vyas, Neha
Ferguson, Charles
Parton, Robert G.
Mayor, Satyajit
author_facet Parchure, Anup
Vyas, Neha
Ferguson, Charles
Parton, Robert G.
Mayor, Satyajit
author_sort Parchure, Anup
collection PubMed
description Hedgehog (Hh) is a secreted morphogen involved in both short- and long-range signaling necessary for tissue patterning during development. It is unclear how this dually lipidated protein is transported over a long range in the aqueous milieu of interstitial spaces. We previously showed that the long-range signaling of Hh requires its oligomerization. Here we show that Hh is secreted in the form of exovesicles. These are derived by the endocytic delivery of cell surface Hh to multivesicular bodies (MVBs) via an endosomal sorting complex required for transport (ECSRT)–dependent process. Perturbations of ESCRT proteins have a selective effect on long-range Hh signaling in Drosophila wing imaginal discs. Of importance, oligomerization-defective Hh is inefficiently incorporated into exovesicles due to its poor endocytic delivery to MVBs. These results provide evidence that nanoscale organization of Hh regulates the secretion of Hh on ESCRT-derived exovesicles, which in turn act as a vehicle for long-range signaling.
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spelling pubmed-46780252016-03-01 Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion Parchure, Anup Vyas, Neha Ferguson, Charles Parton, Robert G. Mayor, Satyajit Mol Biol Cell Articles Hedgehog (Hh) is a secreted morphogen involved in both short- and long-range signaling necessary for tissue patterning during development. It is unclear how this dually lipidated protein is transported over a long range in the aqueous milieu of interstitial spaces. We previously showed that the long-range signaling of Hh requires its oligomerization. Here we show that Hh is secreted in the form of exovesicles. These are derived by the endocytic delivery of cell surface Hh to multivesicular bodies (MVBs) via an endosomal sorting complex required for transport (ECSRT)–dependent process. Perturbations of ESCRT proteins have a selective effect on long-range Hh signaling in Drosophila wing imaginal discs. Of importance, oligomerization-defective Hh is inefficiently incorporated into exovesicles due to its poor endocytic delivery to MVBs. These results provide evidence that nanoscale organization of Hh regulates the secretion of Hh on ESCRT-derived exovesicles, which in turn act as a vehicle for long-range signaling. The American Society for Cell Biology 2015-12-15 /pmc/articles/PMC4678025/ /pubmed/26490120 http://dx.doi.org/10.1091/mbc.E15-09-0671 Text en © 2015 Parchure et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society for Cell Biology.
spellingShingle Articles
Parchure, Anup
Vyas, Neha
Ferguson, Charles
Parton, Robert G.
Mayor, Satyajit
Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
title Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
title_full Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
title_fullStr Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
title_full_unstemmed Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
title_short Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
title_sort oligomerization and endocytosis of hedgehog is necessary for its efficient exovesicular secretion
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4678025/
https://www.ncbi.nlm.nih.gov/pubmed/26490120
http://dx.doi.org/10.1091/mbc.E15-09-0671
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