Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless
Department of Neurobiology
Medical Subject Headings
Animals; Carrier Proteins; Drosophila; Drosophila Proteins; Frizzled Receptors; Intracellular Signaling Peptides and Proteins; Motor Neurons; Nerve Tissue Proteins; Neuromuscular Junction; Protein Transport; Receptors, G-Protein-Coupled; *Signal Transduction; Synapses; Synaptic Vesicles; Wnt1 Protein
Life Sciences | Medicine and Health Sciences | Neuroscience and Neurobiology
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.
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Citation: Cell. 2009 Oct 16;139(2):393-404. Link to article on publisher's site