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

Parchure, Anup, Vyas, Neha, Ferguson, Charles, Parton, Robert G. and Mayor, Satyajit (2015) Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion. Molecular Biology of The Cell, 26 25: 1-35. doi:10.1091/mbc.E15-09-0671

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Author Parchure, Anup
Vyas, Neha
Ferguson, Charles
Parton, Robert G.
Mayor, Satyajit
Title Oligomerization and endocytosis of Hedgehog is necessary for its efficient exovesicular secretion
Journal name Molecular Biology of The Cell   Check publisher's open access policy
ISSN 1939-4586
Publication date 2015-10-21
Year available 2015
Sub-type Article (original research)
DOI 10.1091/mbc.E15-09-0671
Open Access Status File (Publisher version)
Volume 26
Issue 25
Start page 1
End page 35
Total pages 35
Place of publication Bethesda, MD, United States
Publisher American Society for Cell Biology
Language eng
Subject 1312 Molecular Biology
1307 Cell Biology
Abstract 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 had previously shown 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 multi vesicular 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. Importantly 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.
Keyword Cell Biology
Cell Biology
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 1037320
BT/01/COE/09/01
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2016 Collection
Institute for Molecular Bioscience - Publications
Centre for Microscopy and Microanalysis Publications
 
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Created: Thu, 03 Dec 2015, 20:43:30 EST by Susan Allen on behalf of Institute for Molecular Bioscience