title: Proteomic Analysis of Post-synaptic Density Fractions fromShank3Mutant Mice Reveals Brain Region Specific Changes Relevant to Autism Spectrum Disorder.
abstract: Disruption of the humanSHANK3gene can cause several neuropsychiatric disease entities including Phelan-McDermid syndrome, autism spectrum disorder (ASD), and intellectual disability. Although, a wide array of neurobiological studies strongly supports a major role for SHANK3 in organizing the post-synaptic protein scaffold, the molecular processes at synapses of individuals harboringSHANK3mutations are still far from being understood. In this study, we biochemically isolated the post-synaptic density (PSD) fraction from striatum and hippocampus of adultShank3Δ11-/-mutant mice and performed ion-mobility enhanced data-independent label-free LC-MS/MS to obtain the corresponding PSD proteomes (Data are available via ProteomeXchange with identifier PXD005192). This unbiased approach to identify molecular disturbances atShank3mutant PSDs revealed hitherto unknown brain region specific alterations including a striatal decrease of several molecules encoded by ASD susceptibility genes such as the serine/threonine kinase Cdkl5 and the potassium channel KCa1.1. Being the first comprehensive analysis of brain region specific PSD proteomes from aShank3mutant line, our study provides crucial information on molecular alterations that could foster translational treatment studies forSHANK3mutation-associated synaptopathies and possibly also ASD in general.
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm UniversityUlm, Germany; International Graduate School in Molecular Medicine, Ulm UniversityUlm, Germany.
authors.forename: Dominik
authors.initials: D
authors.lastname: Reim
authors.affiliation: Institute for Immunology, University Medical Center of the Johannes-Gutenberg University MainzMainz, Germany; Focus Program Translational Neurosciences, University Medical Center of the Johannes-Gutenberg University MainzMainz, Germany.
authors.forename: Ute
authors.initials: U
authors.lastname: Distler
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm UniversityUlm, Germany; International Graduate School in Molecular Medicine, Ulm UniversityUlm, Germany.
authors.forename: Sonja
authors.initials: S
authors.lastname: Halbedl
authors.affiliation: CNR Neuroscience InstituteMilan, Italy; BIOMETRA, University of MilanMilan, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Verpelli
authors.affiliation: CNR Neuroscience InstituteMilan, Italy; BIOMETRA, University of MilanMilan, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Sala
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University Ulm, Germany.
authors.forename: Juergen
authors.initials: J
authors.lastname: Bockmann
authors.affiliation: Institute for Immunology, University Medical Center of the Johannes-Gutenberg University Mainz Mainz, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tenzer
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm University Ulm, Germany.
authors.forename: Tobias M
authors.initials: TM
authors.lastname: Boeckers
authors.affiliation: Institute for Anatomy and Cell Biology, Ulm UniversityUlm, Germany; Division of Neuroanatomy, Institute of Anatomy, Otto-von-Guericke UniversityMagdeburg, Germany; Leibniz Institute for NeurobiologyMagdeburg, Germany.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Schmeisser
keywords: Homer1; Shank3; autism spectrum disorder; proteome; striatum; synapse