title: Postsynaptic membrane addition depends on the Discs-Large-interacting t-SNARE Gtaxin.
abstract: Targeted membrane addition is a hallmark of many cellular functions. In the nervous system, modification of synaptic membrane size has a major impact on synaptic function. However, because of the complex shape of neurons and the need to target membrane addition to very small and polarized synaptic compartments, this process is poorly understood. Here, we show that Gtaxin (GTX), a Drosophila t-SNARE (target-soluble N-ethylmaleimide-sensitive factor attachment protein receptor), is required for expansion of postsynaptic membranes during new synapse formation. Mutations in gtx lead to drastic reductions in postsynaptic membrane surface, whereas gtx upregulation results in the formation of complex membrane structures at ectopic sites. Postsynaptic GTX activity depends on its direct interaction with Discs-Large (DLG), a multidomain scaffolding protein of the PSD-95 (postsynaptic density protein-95) family with key roles in cell polarity and formation of cellular junctions as well as synaptic protein anchoring and trafficking. We show that DLG selectively determines the postsynaptic distribution of GTX to type I, but not to type II or type III boutons on the same cell, thereby defining sites of membrane addition to this unique set of glutamatergic synapses. We provide a mechanistic explanation for selective targeted membrane expansion at specific synaptic junctions.
authors.affiliation: Department of Neurobiology, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
authors.forename: David
authors.initials: D
authors.lastname: Gorczyca
authors.forename: James
authors.initials: J
authors.lastname: Ashley
authors.forename: Sean
authors.initials: S
authors.lastname: Speese
authors.forename: Norberto
authors.initials: N
authors.lastname: Gherbesi
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thomas
authors.forename: Eckart
authors.initials: E
authors.lastname: Gundelfinger
authors.forename: L Sian
authors.initials: LS
authors.lastname: Gramates
authors.forename: Vivian
authors.initials: V
authors.lastname: Budnik
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D004330:Drosophila; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004351:Drug Resistance; D008969:Molecular Sequence Data; D017729:Presynaptic Terminals / Q000378:metabolism* / Q000502:physiology / Q000648:ultrastructure; D050600:SNARE Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology; D013570:Synaptic Membranes / Q000502:physiology* / Q000648:ultrastructure; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism* / Q000502:physiology
chemical_list: D029721:Drosophila Proteins; D050600:SNARE Proteins; D025521:Tumor Suppressor Proteins; C070350:dlg1 protein, Drosophila