SynDIG4/Prrt1 Is Required for Excitatory Synapse Development and Plasticity Underlying Cognitive Function

Cell Reports
Lucas MattElva Díaz

Abstract

Altering AMPA receptor (AMPAR) content at synapses is a key mechanism underlying the regulation of synaptic strength during learning and memory. Previous work demonstrated that SynDIG1 (synapse differentiation-induced gene 1) encodes a transmembrane AMPAR-associated protein that regulates excitatory synapse strength and number. Here we show that the related protein SynDIG4 (also known as Prrt1) modifies AMPAR gating properties in a subunit-dependent manner. Young SynDIG4 knockout (KO) mice have weaker excitatory synapses, as evaluated by immunocytochemistry and electrophysiology. Adult SynDIG4 KO mice show complete loss of tetanus-induced long-term potentiation (LTP), while mEPSC amplitude is reduced by only 25%. Furthermore, SynDIG4 KO mice exhibit deficits in two independent cognitive assays. Given that SynDIG4 colocalizes with the AMPAR subunit GluA1 at non-synaptic sites, we propose that SynDIG4 maintains a pool of extrasynaptic AMPARs necessary for synapse development and function underlying higher-order cognitive plasticity.

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Citations

Nov 15, 2018·Frontiers in Cellular Neuroscience·Brian G HiesterMatthew J Kennedy
Apr 3, 2019·Cellular and Molecular Life Sciences : CMLS·Diane BissenAmparo Acker-Palmer
Feb 1, 2020·The Journal of Physiology·Aichurok Kamalova, Terunaga Nakagawa
Feb 16, 2019·Frontiers in Molecular Neuroscience·Lucas MattJohannes W Hell
Oct 1, 2020·Developmental Neurobiology·Delphine GobertEdward S Ruthazer
Feb 4, 2021·The Journal of Physiology·Stuart G Cull-Candy, Mark Farrant
Feb 25, 2021·Translational Neuroscience·Min LiXuezhen Wang
Apr 24, 2021·Current Opinion in Pharmacology·Mazyar Abdollahi NejatAugust B Smit
Jun 26, 2021·Journal of Psychiatric Research·Zeinab Shirvani-FarsaniIman Sadeghi
Jul 17, 2021·Neuropharmacology·Peter M MatthewsIngo H Greger
Aug 20, 2021·Frontiers in Synaptic Neuroscience·Emily Eischen MartinMohiuddin Ahmad
Aug 27, 2021·Cellular and Molecular Neurobiology·Qing-Lin WuNai-Hong Chen
Sep 30, 2021·The Journal of Physiology·Niccolò P Pampaloni, Andrew J R Plested
Dec 18, 2021·Journal of Proteome Research·Manhong XuJoyce Tombran-Tink

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