Glutamate signaling at cytoneme synapses

We investigated the roles of neuronal synapse components for development of the Drosophila air sac primordium (ASP). The ASP, an epithelial tube, extends specialized signaling filopodia called cytonemes that take up signals such as Dpp from the wing imaginal disc. Dpp signaling in the ASP requires that disc cells express Dpp, Synaptobrevin, Synaptotagmin-1, the glutamate transporter, and a voltage-gated calcium channel, and that ASP cells express the Dpp receptor, Synaptotagmin-4 and the AMPA-type glutamate receptor GluRII. Calcium transients in ASP cytonemes correlate with signaling activity. Calcium transients in the ASP require GluRII, are activated by L-glutamate and by stimulation of an optogenetic ion channel expressed in the wing disc, and are inhibited by EGTA and NASPM. Activation of GluRII is essential but not sufficient for signaling. Cytoneme-mediated signaling is glutamatergic. Summary Paracrine signals transfer between Drosophila epithelial cells at glutamatergic synapses.