title: Concerted action of zinc and ProSAP/Shank in synaptogenesis and synapse maturation.
abstract: Neuronal morphology and number of synapses is not static, but can change in response to a variety of factors, a process called synaptic plasticity. These structural and molecular changes are believed to represent the basis for learning and memory, thereby underling both the developmental and activity-dependent remodelling of excitatory synapses. Here, we report that Zn(2+) ions, which are highly enriched within the postsynaptic density (PSD), are able to influence the recruitment of ProSAP/Shank proteins to PSDs in a family member-specific manner during the course of synaptogenesis and synapse maturation. Through selectively overexpressing each family member at excitatory postsynapses and comparing this to shRNA-mediated knockdown, we could demonstrate that only the overexpression of zinc-sensitive ProSAP1/Shank2 or ProSAP2/Shank3 leads to increased synapse density, although all of them cause a decrease upon knockdown. Furthermore, depletion of synaptic Zn(2+) along with the knockdown of zinc-insensitive Shank1 causes the rapid disintegration of PSDs and the loss of several postsynaptic molecules including Homer1, PSD-95 and NMDA receptors. These findings lead to the model that the concerted action of ProSAP/Shank and Zn(2+) is essential for the structural integrity of PSDs and moreover that it is an important element of synapse formation, maturation and structural plasticity.
authors.affiliation: Institute of Anatomy and Cell Biology, University of Ulm, Ulm, Germany.
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Grabrucker
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Knight
authors.forename: Christian
authors.initials: C
authors.lastname: Proepper
authors.forename: Juergen
authors.initials: J
authors.lastname: Bockmann
authors.forename: Marisa
authors.initials: M
authors.lastname: Joubert
authors.forename: Magali
authors.initials: M
authors.lastname: Rowan
authors.forename: G Uirich
authors.initials: GU
authors.lastname: Nienhaus
authors.forename: Craig C
authors.initials: CC
authors.lastname: Garner
authors.forename: Jim U
authors.initials: JU
authors.lastname: Bowie
authors.forename: Michael R
authors.initials: MR
authors.lastname: Kreutz
authors.forename: Eckart D
authors.initials: ED
authors.lastname: Gundelfinger
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002614:Chelating Agents; D002850:Chromatography, Gel; D006624:Hippocampus / Q000166:cytology*; D007150:Immunohistochemistry; D046529:Microscopy, Electron, Transmission; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D009841:Oligonucleotides / Q000235:genetics; D057907:Post-Synaptic Density / Q000378:metabolism*; D015363:Quinolones; D034622:RNA Interference; D051381:Rats; D013569:Synapses / Q000502:physiology*; D014105:Tosyl Compounds; D014162:Transfection; D015032:Zinc / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002614:Chelating Agents; D009419:Nerve Tissue Proteins; D009841:Oligonucleotides; D015363:Quinolones; C485686:Shank2 protein, rat; C120532:Shank3 protein, rat; D014105:Tosyl Compounds; D015032:Zinc; C084731:zinquin