Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion : Nature Communications : Nature Publishing Group

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion : Nature Communications : Nature Publishing Group

Exosomes as Hedgehog carriers in cytoneme-mediated transport and secretion

• Ana-Citlali Gradilla,
• Esperanza González,
• Irene Seijo,
• German Andrés,
• Marcus Bischoff,
• Laura González-Mendez,
• Vanessa Sánchez,
• Ainhoa Callejo,
• Carmen Ibáñez,
• Milagros Guerra,
• João Ramalho Ortigão-Farias,
• James D. Sutherland,
• Monika González,
• Rosa Barrio,
• Juan M. Falcón-Pérez
• & Isabel Guerrero

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Nature Communications

 

5,

 

Article number:

 

5649

 

doi:10.1038/ncomms6649

Received

 

31 January 2014 

Accepted

 

22 October 2014 

Published

 

04 December 2014

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Abstract

• Abstract• 
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The Hedgehog signalling pathway is crucial for development, adult stem cell maintenance, cell migration and axon guidance in a wide range of organisms. During development, the ​Hhmorphogen directs tissue patterning according to a concentration gradient. Lipid modifications on ​Hh are needed to achieve graded distribution, leading to debate about how ​Hh is transported to target cells despite being membrane-tethered. Cytonemes in the region of ​Hh signalling have been shown to be essential for gradient formation, but the carrier of the morphogen is yet to be defined. Here we show that ​Hh and its co-receptor ​Ihog are in exovesicles transported via cytonemes. These exovesicles present protein markers and other features of exosomes. Moreover, the cell machinery for exosome formation is necessary for normal ​Hh secretion and graded signalling. We propose ​Hh transport via exosomes along cytonemes as a significant mechanism for the restricted distribution of a lipid-modified morphogen.