Porcupine Controls Hippocampal AMPAR Levels, Composition, and Synaptic Transmission

Cell Reports
Nadine ErlenhardtDavid S Bredt

Abstract

AMPA receptor (AMPAR) complexes contain auxiliary subunits that modulate receptor trafficking and gating. In addition to the transmembrane AMPAR regulatory proteins (TARPs) and cornichons (CNIH-2/3), recent proteomic studies identified a diverse array of additional AMPAR-associated transmembrane and secreted partners. We systematically surveyed these and found that PORCN and ABHD6 increase GluA1 levels in transfected cells. Knockdown of PORCN in rat hippocampal neurons, which express it in high amounts, selectively reduces levels of all tested AMPAR complex components. Regulation of AMPARs is independent of PORCN's membrane-associated O-acyl transferase activity. PORCN knockdown in hippocampal neurons decreases AMPAR currents and accelerates desensitization and leads to depletion of TARP γ-8 from AMPAR complexes. Conditional PORCN knockout mice also exhibit specific changes in AMPAR expression and gating that reduce basal synaptic transmission but leave long-term potentiation intact. These studies define additional roles for PORCN in controlling synaptic transmission by regulating the level and composition of hippocampal AMPAR complexes.

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Citations

Feb 18, 2017·ACS Chemical Neuroscience·Anthony J Baucum
Oct 30, 2018·Glia·Andrea MöldersNikolaj Klöcker
Jan 31, 2018·The EMBO Journal·Kathrin GlaeserMichael Boutros
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Feb 1, 2020·The Journal of Physiology·Aichurok Kamalova, Terunaga Nakagawa
Aug 24, 2018·Frontiers in Molecular Neuroscience·Esther Gratacòs-BatlleDavid Soto
Apr 3, 2019·Cellular and Molecular Life Sciences : CMLS·Diane BissenAmparo Acker-Palmer
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Jan 15, 2021·British Journal of Pharmacology·Cristina MiralpeixRosalía Rodríguez-Rodríguez
Jul 17, 2021·Neuropharmacology·Peter M MatthewsIngo H Greger

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