title: A perisynaptic ménage à trois between Dlg, DLin-7, and Metro controls proper organization of Drosophila synaptic junctions.
abstract: Structural plasticity of synaptic junctions is a prerequisite to achieve and modulate connectivity within nervous systems, e.g., during learning and memory formation. It demands adequate backup systems that allow remodeling while retaining sufficient stability to prevent unwanted synaptic disintegration. The strength of submembranous scaffold complexes, which are fundamental to the architecture of synaptic junctions, likely constitutes a crucial determinant of synaptic stability. Postsynaptic density protein-95 (PSD-95)/ Discs-large (Dlg)-like membrane-associated guanylate kinases (DLG-MAGUKs) are principal scaffold proteins at both vertebrate and invertebrate synapses. At Drosophila larval glutamatergic neuromuscular junctions (NMJs) DlgA and DlgS97 exert pleiotropic functions, probably reflecting a few known and a number of yet-unknown binding partners. In this study we have identified Metro, a novel p55/MPP-like Drosophila MAGUK as a major binding partner of perisynaptic DlgS97 at larval NMJs. Based on homotypic LIN-2,-7 (L27) domain interactions, Metro stabilizes junctional DlgS97 in a complex with the highly conserved adaptor protein DLin-7. In a remarkably interdependent manner, Metro and DLin-7 act downstream of DlgS97 to control NMJ expansion and proper establishment of synaptic boutons. Using quantitative 3D-imaging we further demonstrate that the complex controls the size of postsynaptic glutamate receptor fields. Our findings accentuate the importance of perisynaptic scaffold complexes for synaptic stabilization and organization.
authors.affiliation: Institut für Genetik, Heinrich-Heine-Universität Düsseldorf, D-40225 Düsseldorf, Germany.
authors.forename: André
authors.initials: A
authors.lastname: Bachmann
authors.forename: Oliver
authors.initials: O
authors.lastname: Kobler
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Kittel
authors.forename: Carolin
authors.initials: C
authors.lastname: Wichmann
authors.forename: Jimena
authors.initials: J
authors.lastname: Sierralta
authors.forename: Stephan J
authors.initials: SJ
authors.lastname: Sigrist
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Knust
authors.forename: Ulrich
authors.initials: U
authors.lastname: Thomas
mesh_terms: D000483:Alleles; D000818:Animals; D030801:Animals, Genetically Modified; D029681:Arabidopsis Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins; D051528:Guanylate Kinases / Q000235:genetics / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D018613:Microscopy, Confocal; D009154:Mutation; D009469:Neuromuscular Junction / Q000254:growth & development / Q000502:physiology*; D017729:Presynaptic Terminals / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D017470:Receptors, Glutamate / Q000378:metabolism; D017385:Sequence Homology; D013049:Spectrin / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology
chemical_list: D029681:Arabidopsis Proteins; D029721:Drosophila Proteins; D012333:RNA, Messenger; D017470:Receptors, Glutamate; D013049:Spectrin; D051528:Guanylate Kinases; C549540:metro protein, Drosophila