Trans-synaptic transmission of vesicular Wnt signals through Evi/Wntless.
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.
Korkut
Ceren
C
Department of Neurobiology, University of Massachusetts Medical School, Worcester, MA 01655, USA.
Ataman
Bulent
B
Ramachandran
Preethi
P
Ashley
James
J
Barria
Romina
R
Gherbesi
Norberto
N
Budnik
Vivian
V
D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D004330:Drosophila / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D051157:Frizzled Receptors / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008565:Membrane Proteins; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009469:Neuromuscular Junction; D021381:Protein Transport; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism; D015398:Signal Transduction; D013569:Synapses; D013572:Synaptic Vesicles / Q000378:metabolism*; D051155:Wnt1 Protein / Q000378:metabolism*
D002352:Carrier Proteins; D029721:Drosophila Proteins; D051157:Frizzled Receptors; C491307:Grip protein, Drosophila; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D043562:Receptors, G-Protein-Coupled; C511046:Wls protein, Drosophila; D051155:Wnt1 Protein; C101703:fz2 protein, Drosophila; C074622:wg protein, Drosophila