Impaired PtdIns(4,5)P2 synthesis in nerve terminals produces defects in synaptic vesicle trafficking

Nature
Gilbert Di PaoloPietro De Camilli

Abstract

Phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) has an important function in cell regulation both as a precursor of second messenger molecules and by means of its direct interactions with cytosolic and membrane proteins. Biochemical studies have suggested a role for PtdIns(4,5)P2 in clathrin coat dynamics, and defects in its dephosphorylation at the synapse produce an accumulation of coated endocytic intermediates. However, the involvement of PtdIns(4,5)P2 in synaptic vesicle exocytosis remains unclear. Here, we show that decreased levels of PtdIns(4,5)P2 in the brain and an impairment of its depolarization-dependent synthesis in nerve terminals lead to early postnatal lethality and synaptic defects in mice. These include decreased frequency of miniature currents, enhanced synaptic depression, a smaller readily releasable pool of vesicles, delayed endocytosis and slower recycling kinetics. Our results demonstrate a critical role for PtdIns(4,5)P2 synthesis in the regulation of multiple steps of the synaptic vesicle cycle.

References

Apr 1, 1988·Proceedings of the National Academy of Sciences of the United States of America·S M AudigierP Greengard
Jan 31, 1995·Proceedings of the National Academy of Sciences of the United States of America·C F Stevens, T Tsujimoto
Aug 1, 1994·Seminars in Cell Biology·F Valtorta, J Meldolesi
Jan 25, 1996·Nature·P S McPhersonP De Camilli
Mar 15, 1996·Science·P De CamilliP Novick
Jun 1, 1996·The Journal of Cell Biology·K TakeiP De Camilli
Nov 13, 1999·Nature Cell Biology·R Fesce, J Meldolesi
Apr 27, 2000·Nature Cell Biology·S Sankaranarayanan, T A Ryan
Aug 10, 2000·The Journal of Cell Biology·T W HarrisE M Jorgensen
Feb 15, 2001·Nature Neuroscience·S Sankaranarayanan, T A Ryan
Jul 17, 2001·Current Opinion in Cell Biology·T F Martin
Dec 6, 2001·Science's STKE : Signal Transduction Knowledge Environment·D W HilgemannC Nasuhoglu
Sep 28, 2002·Nature·Marijn G J FordHarvey T McMahon
Dec 14, 2002·Proceedings of the National Academy of Sciences of the United States of America·Warren T KimPietro De Camilli
Dec 31, 2002·Current Opinion in Structural Biology·Philip R Evans, David J Owen
Jan 9, 2003·Annual Review of Physiology·Michael P Czech
Jun 6, 2003·Nature·Sunil P Gandhi, Charles F Stevens
Aug 12, 2003·Nature Neuroscience·Kristina D MichevaStephen J Smith
Aug 20, 2003·The Journal of Cell Biology·Yoshikatsu Aikawa, Thomas F J Martin
Sep 23, 2003·The Journal of Membrane Biology·R L DoughmanR A Anderson
Oct 7, 2003·Annual Review of Neuroscience·Venkatesh N Murthy, Pietro De Camilli
Nov 19, 2003·Neuron·Patrik VerstrekenHugo J Bellen

❮ Previous
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Citations

Jun 2, 2007·Pflügers Archiv : European journal of physiology·Ioannis E MichailidisJian Yang
May 24, 2007·Pflügers Archiv : European journal of physiology·Yuntao S Mao, Helen L Yin
Nov 26, 2010·Pflügers Archiv : European journal of physiology·Ioannis E MichailidisLia Baki
Jan 22, 2010·Protoplasma·Till IschebeckIngo Heilmann
Jun 13, 2013·Trends in Cell Biology·Dmytro Puchkov, Volker Haucke
Oct 10, 2006·Nature Cell Biology·Seok-Yong ChoiMichael A Frohman
Apr 24, 2010·Nature Reviews. Cancer·Tom D Bunney, Matilda Katan
Feb 3, 2005·Nature Reviews. Neuroscience·Jeffrey Rohrbough, Kendal Broadie
Jul 2, 2008·Proceedings of the National Academy of Sciences of the United States of America·Sergey V VoronovGilbert Di Paolo
Sep 6, 2008·Proceedings of the National Academy of Sciences of the United States of America·Yanfeng WangCharles S Abrams
Nov 7, 2008·Proceedings of the National Academy of Sciences of the United States of America·Liang-Wei Gong, Pietro De Camilli
Oct 7, 2009·Proceedings of the National Academy of Sciences of the United States of America·Karen T Chang, Kyung-Tai Min
Jan 19, 2010·Proceedings of the National Academy of Sciences of the United States of America·Marzuk M KamalJonathon Howard
Oct 19, 2011·Proceedings of the National Academy of Sciences of the United States of America·Takuma KishimotoDavid G Drubin
Feb 7, 2012·Proceedings of the National Academy of Sciences of the United States of America·Xuelin LouPietro De Camilli
Aug 15, 2012·Proceedings of the National Academy of Sciences of the United States of America·Laura RodriguezFabio Mammano
Jun 27, 2013·Proceedings of the National Academy of Sciences of the United States of America·Florian BuchmayerHarald H Sitte
Jan 26, 2010·The Journal of Biological Chemistry·Leslie A CaromileDaniel F Bowen-Pope
Nov 12, 2009·The Journal of Biological Chemistry·Nina KahlfeldtVolker Haucke
Jul 14, 2010·The Journal of Biological Chemistry·Laura A Volpicelli-DaleyPietro De Camilli
Jul 20, 2012·The Journal of Biological Chemistry·Daniel ParisottoThomas H Söllner
Jan 10, 2013·The Journal of Biological Chemistry·Tingting ZhuWei Zou
Mar 17, 2009·The Journal of Biological Chemistry·James R ThiemanLinton M Traub
Mar 16, 2005·The Journal of Experimental Medicine·Junko SasakiYasunori Kanaho
Nov 18, 2005·Molecular Biology of the Cell·David PadrónMichael G Roth
Apr 25, 2008·Molecular Biology of the Cell·Dong-Won LeeLois E Greene
Apr 19, 2012·Human Molecular Genetics·Jack-Christophe CossecMarie-Claude Potier
Dec 23, 2004·Science's STKE : Signal Transduction Knowledge Environment·Thierry Galli, Volker Haucke
Jul 7, 2009·Annual Review of Cell and Developmental Biology·Jeremy Dittman, Timothy A Ryan
Oct 11, 2005·Annual Review of Cell and Developmental Biology·Verena Niggli
May 30, 2008·American Journal of Physiology. Renal Physiology·Michael B ButterworthJohn P Johnson
Feb 7, 2009·Physiology·Heather J McCrea, Pietro De Camilli
Dec 13, 2007·Blood·Federica MicucciRicciarda Galandrini

❮ Previous
Next ❯

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