title: The postsynaptic t-SNARE Syntaxin 4 controls traffic of Neuroligin 1 and Synaptotagmin 4 to regulate retrograde signaling.
abstract: Postsynaptic cells can induce synaptic plasticity through the release of activity-dependent retrograde signals. We previously described a Ca(2+)-dependent retrograde signaling pathway mediated by postsynaptic Synaptotagmin 4 (Syt4). To identify proteins involved in postsynaptic exocytosis, we conducted a screen for candidates that disrupted trafficking of a pHluorin-tagged Syt4 at Drosophila neuromuscular junctions (NMJs). Here we characterize one candidate, the postsynaptic t-SNARE Syntaxin 4 (Syx4). Analysis of Syx4 mutants reveals that Syx4 mediates retrograde signaling, modulating the membrane levels of Syt4 and the transsynaptic adhesion protein Neuroligin 1 (Nlg1). Syx4-dependent trafficking regulates synaptic development, including controlling synaptic bouton number and the ability to bud new varicosities in response to acute neuronal stimulation. Genetic interaction experiments demonstrate Syx4, Syt4, and Nlg1 regulate synaptic growth and plasticity through both shared and parallel signaling pathways. Our findings suggest a conserved postsynaptic SNARE machinery controls multiple aspects of retrograde signaling and cargo trafficking within the postsynaptic compartment.
authors.affiliation: The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States.|Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Kathryn P
authors.identifier: 0000-0003-1769-2587
authors.initials: KP
authors.lastname: Harris
authors.affiliation: The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States.|Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Yao V
authors.initials: YV
authors.lastname: Zhang
authors.affiliation: The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States.|Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Piccioli
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, United States.|Howard Hughes Medical Institute, Harvard Medical School, Boston, United States.
authors.forename: Norbert
authors.initials: N
authors.lastname: Perrimon
authors.affiliation: The Picower Institute for Learning and Memory, Massachusetts Institute of Technology, Cambridge, United States.|Department of Biology, Massachusetts Institute of Technology, Cambridge, United States.|Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, United States.
authors.forename: J Troy
authors.identifier: 0000-0001-5576-2887
authors.initials: JT
authors.lastname: Littleton
mesh_terms: D000818:Animals; D015816:Cell Adhesion Molecules, Neuronal / Q000378:metabolism*; D004252:DNA Mutational Analysis; D004330:Drosophila; D005089:Exocytosis; D050505:Mutant Proteins / Q000235:genetics / Q000378:metabolism; D009469:Neuromuscular Junction / Q000378:metabolism*; D009473:Neuronal Plasticity; D050765:Qa-SNARE Proteins / Q000235:genetics / Q000378:metabolism*; D050857:Synaptotagmins / Q000378:metabolism*
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; D050505:Mutant Proteins; D050765:Qa-SNARE Proteins; C093438:neuroligin 1; D050857:Synaptotagmins
keywords: D. melanogaster; Neuroligin; Synaptotagmin 4; Syntaxin 4; cell biology; neuroscience; synapse; synaptic plasticity