Format

Send to

Choose Destination
Mol Biol Cell. 2015 Dec 15;26(25):4700-17. doi: 10.1091/mbc.E15-09-0671. Epub 2015 Oct 21.

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

Author information

1
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India.
2
Institute for Stem Cell Biology and Regenerative Medicine, Tata Institute of Fundamental Research, Bangalore 560065, India.
3
Institute for Molecular Bioscience and Centre for Microscopy and Microanalysis, University of Queensland, Brisbane St Lucia 4072, Australia.
4
National Centre for Biological Sciences, Tata Institute of Fundamental Research, Bangalore 560065, India Institute for Stem Cell Biology and Regenerative Medicine, Tata Institute of Fundamental Research, Bangalore 560065, India mayor@ncbs.res.in.

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 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.

PMID:
26490120
PMCID:
PMC4678025
DOI:
10.1091/mbc.E15-09-0671
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Atypon Icon for PubMed Central
Loading ...
Support Center