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PMID: 19837038 Published · ppublish English Journal Article Research Support, N.I.H., Extramural

Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless.

Cell ·Vol. 139 ·No. 2 ·2009-10-16 ·Pages 393-404

Korkut C, Ataman B, Ramachandran P, Ashley J, Barria R, Gherbesi N, Budnik V

Abstract

Wnts play pivotal roles during development and in the mature nervous system. However, the mechanism by which Wnts traffic between cells has remained elusive. Here we demonstrate a mechanism of Wnt transmission through release of exosome-like vesicles containing the Wnt-binding protein Evenness Interrupted/Wntless/Sprinter (Evi/Wls/Srt). We show that at the Drosophila larval neuromuscular junction (NMJ), presynaptic vesicular release of Evi is required for the secretion of the Wnt, Wingless (Wg). We also show that Evi acts cell-autonomously in the postsynaptic Wnt-receiving cell to target dGRIP, a Wg-receptor-interacting protein, to postsynaptic sites. Upon Evi loss of function, dGRIP is not properly targeted to synaptic sites, interfering with postsynaptic Wnt signal transduction. These findings uncover a previously unknown cellular mechanism by which a secreted Wnt is transported across synapses by Evi-containing vesicles and reveal trafficking functions of Evi in both the Wnt-producing and the Wnt-receiving cells. For a video summary of this article, see the PaperFlick file with the Supplemental Data available online.

MeSH Terms
Animals Carrier Proteins/metabolism Drosophila/metabolism Drosophila Proteins/metabolism Frizzled Receptors/metabolism Intracellular Signaling Peptides and Proteins/metabolism Membrane Proteins Motor Neurons/metabolism Nerve Tissue Proteins/metabolism Neuromuscular Junction Protein Transport Receptors, G-Protein-Coupled/metabolism Signal Transduction Synapses Synaptic Vesicles/metabolism Wnt1 Protein/metabolism
Chemicals
Carrier Proteins Drosophila Proteins Frizzled Receptors Grip protein, Drosophila Intracellular Signaling Peptides and Proteins Membrane Proteins Nerve Tissue Proteins Receptors, G-Protein-Coupled Wls protein, Drosophila Wnt1 Protein fz2 protein, Drosophila wg protein, Drosophila
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Korkut Ceren
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Ataman Bulent
Ramachandran Preethi
Ashley James
Barria Romina
Gherbesi Norberto
Budnik Vivian
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2009.07.051
Published
2009-10-16
Pages
393-404
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC2785045
Subset
IM
Grants
NIDDK NIH HHS · P30 DK032520 · United States
NIMH NIH HHS · R01 MH070000 · United States
NIMH NIH HHS · R01 MH070000-06 · United States
NIDDK NIH HHS · DK32520 · United States
Corrections
CommentIn
PMID: 19837027
External Links
PubMed source DOI: 10.1016/j.cell.2009.07.051 PMC Full Text View journal details
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