GSK3α, not GSK3β, drives hippocampal NMDAR-dependent LTD via tau-mediated spine anchoring.

The EMBO Journal
Jonathan E DraffinJosé A Esteban

Abstract

Glycogen synthase kinase-3 (GSK3) is an important signalling protein in the brain and modulates different forms of synaptic plasticity. Neuronal functions of GSK3 are typically attributed to one of its two isoforms, GSK3β, simply because of its prevalent expression in the brain. Consequently, the importance of isoform-specific functions of GSK3 in synaptic plasticity has not been fully explored. We now directly address this question for NMDA receptor-dependent long-term depression (LTD) in the hippocampus. Here, we specifically target the GSK3 isoforms with shRNA knock-down in mouse hippocampus and with novel isoform-selective drugs to dissect their roles in LTD. Using electrophysiological and live imaging approaches, we find that GSK3α, but not GSK3β, is required for LTD. The specific engagement of GSK3α occurs via its transient anchoring in dendritic spines during LTD induction. We find that the major GSK3 substrate, the microtubule-binding protein tau, is required for this spine anchoring of GSK3α and mediates GSK3α-induced LTD. These results link GSK3α and tau in a common mechanism for synaptic depression and rule out a major role for GSK3β in this process.

References

May 15, 1992·Proceedings of the National Academy of Sciences of the United States of America·S M Dudek, M F Bear
Apr 1, 1991·Journal of Neuroscience Methods·L StoppiniD Muller
Jan 7, 1993·Nature·T V Bliss, G L Collingridge
Dec 2, 2000·Nature Neuroscience·E C BeattieR C Malenka
Aug 31, 2001·Progress in Neurobiology·C A Grimes, R S Jope
Sep 27, 2001·Proceedings of the National Academy of Sciences of the United States of America·C H KimR L Huganir
Nov 15, 2001·The Journal of Biological Chemistry·Elizabeth FraserTrevor C Dale
Jan 29, 2002·The Journal of Biological Chemistry·Wei SunHemant K Paudel
Feb 28, 2002·The Journal of Biological Chemistry·Denise M Ferkey, David Kimelman
Jun 6, 2002·Journal of Chemical Neuroanatomy·Hong-Bing YaoDavid Chi-Cheong Wan
Jun 11, 2002·The Journal of Biological Chemistry·Christina N BennettOrmond A MacDougald
Aug 21, 2003·The Journal of Biological Chemistry·Ratan BhatJesús Avila
Jul 30, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·W Timothy O'BrienPeter S Klein
Sep 10, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Peter V MasseyZafar I Bashir
Jun 14, 2005·Brain Research. Molecular Brain Research·Paul C ChinSantosh R D'Mello
Jan 24, 2007·The European Journal of Neuroscience·Claudie HooperSimon Lovestone
Mar 3, 2007·Neuron·Stéphane PeineauGraham L Collingridge
Apr 18, 2007·The Journal of Biological Chemistry·Gordon P Meares, Richard S Jope
May 10, 2007·Nature Protocols·Josef BischofbergerPeter Jonas
Jun 16, 2007·Cell·Rune LindingTony Pawson
Oct 3, 2007·Cell Metabolism·Katrina MacAulayJames R Woodgett
Nov 9, 2007·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Ling-Qiang ZhuJian-Zhi Wang
Feb 9, 2008·The American Journal of Pathology·Dick TerwelFred Van Leuven
Aug 13, 2008·Molecular and Cellular Biology·Satish PatelJames R Woodgett
Oct 30, 2008·PloS One·Tetsuya KimuraAkihiko Takashima
Mar 7, 2009·Molecular Cancer·Tae-Yeon Eom, Richard S Jope
Oct 6, 2009·Nature Neuroscience·Woo-Yang KimWilliam D Snider
Nov 21, 2009·Molecular Brain·Oksana Kaidanovich-BeilinJames R Woodgett
Dec 17, 2009·Neurobiology of Disease·Elena Gómez de BarredaJesús Avila

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Citations

Dec 20, 2020·Biomolecules·Octavio Silva-GarcíaVíctor M Baizabal-Aguirre
Apr 4, 2021·Cells·Carmen Laura Sayas, Jesús Ávila

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