title: Presynaptic PI3K activity triggers the formation of glutamate receptors at neuromuscular terminals of Drosophila.
abstract: Synapse transmission depends on the precise structural and functional assembly between pre- and postsynaptic elements. This tightly regulated interaction has been thoroughly characterised in vivo in the Drosophila glutamatergic larval neuromuscular junction (NMJ) synapse, a suitable model to explore synapse formation, dynamics and plasticity. Previous findings have demonstrated that presynaptic upregulation of phosphoinositide 3-kinase (PI3K) increases synapse number, generating new functional contacts and eliciting changes in behaviour. Here, we show that genetically driven overexpression of PI3K in the presynaptic element also leads to a correlated increase in the levels of glutamate receptor (GluRII) subunits and the number of postsynaptic densities (PSDs), without altering GluRII formation and assembly dynamics. In addition to GluRIIs, presynaptic PI3K activity also modifies the expression of the postsynaptic protein Discs large (Dlg). Remarkably, PI3K specifically overexpressed in the final larval stages is sufficient for the formation of NMJ synapses. No differences in the number of synapses and PSDs were detected when PI3K was selectively expressed in the postsynaptic compartment. Taken together, these results demonstrate that PI3K-dependent synaptogenesis plays an instructive role in PSD formation and growth from the presynaptic side.
authors.affiliation: Cajal Institute, Consejo Superior de Investigaciones Científicas, Ave Dr Arce 37, Madrid 28002, Spain.
authors.forename: Sheila
authors.initials: S
authors.lastname: Jordán-Álvarez
authors.forename: Wernher
authors.initials: W
authors.lastname: Fouquet
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
authors.forename: Angel
authors.initials: A
authors.lastname: Acebes
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism; D004331:Drosophila melanogaster / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D007150:Immunohistochemistry; D009469:Neuromuscular Junction / Q000201:enzymology / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000096:biosynthesis* / Q000378:metabolism; D013569:Synapses / Q000201:enzymology / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis / Q000235:genetics
chemical_list: D029721:Drosophila Proteins; C557617:GAL4 protein, Drosophila; D017470:Receptors, Glutamate; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila; D019869:Phosphatidylinositol 3-Kinases