Genetic analysis of synaptotagmin 2 in spontaneous and Ca2+-triggered neurotransmitter release.

The EMBO Journal
Zhiping P PangThomas C Südhof

Abstract

Synaptotagmin 2 resembles synaptotagmin 1, the Ca2+ sensor for fast neurotransmitter release in forebrain synapses, but little is known about synaptotagmin 2 function. Here, we describe a severely ataxic mouse strain that harbors a single, destabilizing amino-acid substitution (I377N) in synaptotagmin 2. In Calyx of Held synapses, this mutation causes a delay and a decrease in Ca2+-induced but not in hypertonic sucrose-induced release, suggesting that synaptotagmin 2 mediates Ca2+ triggering of evoked release in brainstem synapses. Unexpectedly, we additionally observed in synaptotagmin 2 mutant synapses a dramatic increase in spontaneous release. Synaptotagmin 1-deficient excitatory and inhibitory cortical synapses also displayed a large increase in spontaneous release, demonstrating that this effect was shared among synaptotagmins 1 and 2. Our data suggest that synaptotagmin 1 and 2 perform equivalent functions in the Ca2+ triggering of action potential-induced release and in the restriction of spontaneous release, consistent with a general role of synaptotagmins in controlling 'release slots' for synaptic vesicles at the active zone.

References

Oct 25, 1994·Proceedings of the National Academy of Sciences of the United States of America·K BroadieT L Schwarz
Dec 1, 1994·Neuron·B UllrichT C Südhof
Mar 10, 2001·Nature·R Fernández-ChacónT C Südhof
May 16, 2001·Biochemistry·J UbachJ Rizo
Jun 11, 2002·Nature Neuroscience·Ok-Ho ShinThomas C Südhof
Nov 8, 2002·American Journal of Pharmacogenomics : Genomics-related Research in Drug Development and Clinical Practice·Gabriele StummMichael Nehls
Dec 7, 2002·Neuron·Motojiro Yoshihara, J Troy Littleton
Jan 28, 2003·Drug Discovery Today·Andreas RussMichael Nehls
Aug 27, 2003·The Journal of General Physiology·Jakob B SørensenErwin Neher
Jul 9, 2004·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Tei-ichi Nishiki, George J Augustine
Mar 29, 2005·Proceedings of the National Academy of Sciences of the United States of America·Enfu HuiEdwin R Chapman
Jan 13, 2006·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Gábor NagyJakob B Sørensen

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Citations

Aug 10, 2006·Cell and Tissue Research·Ralf Schneggenburger, Ian D Forsythe
May 22, 2013·Current Neurology and Neuroscience Reports·Shawn P AlterGary W Miller
Nov 30, 2007·Nature·Jianyuan SunThomas C Südhof
Jan 13, 2009·Nature Neuroscience·Zhenjie ZhangMeyer B Jackson
May 5, 2009·Nature Neuroscience·Jun XuThomas C Südhof
Dec 11, 2007·Nature Neuroscience·Jianhua XuLing-Gang Wu
May 23, 2008·Nature Reviews. Molecular Cell Biology·Sascha Martens, Harvey T McMahon
Jul 16, 2008·Nature Structural & Molecular Biology·Michael C ChickaEdwin R Chapman
Mar 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Natalia GustavssonWeiping Han
Mar 1, 2008·Proceedings of the National Academy of Sciences of the United States of America·Jean-Sébastien SchonnJakob B Sørensen
Jul 21, 2010·Proceedings of the National Academy of Sciences of the United States of America·Hua WenPaul Brehm
Oct 20, 2010·Proceedings of the National Academy of Sciences of the United States of America·Margarita SegoviaGuillermo Alvarez de Toledo
Aug 24, 2010·The Journal of Biological Chemistry·Zhiping P PangThomas C Südhof
May 30, 2008·The Journal of Biological Chemistry·Akhil BhallaEdwin R Chapman
Jun 14, 2008·The Journal of Pharmacology and Experimental Therapeutics·Wei HuBoris Tabakoff
Aug 16, 2008·Science·Stefan H GerberThomas C Südhof
Feb 13, 2010·Science·Alexander J GroffenMatthijs Verhage
Feb 16, 2008·Annual Review of Biochemistry·Edwin R Chapman
Jan 10, 2008·Annual Review of Cell and Developmental Biology·Jakob B Sørensen
Jul 25, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Brie E PaddockNoreen E Reist
Jun 12, 2009·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Huisheng LiuEdwin R Chapman
Oct 3, 2008·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Deniz AtasoyEge T Kavalali
Oct 12, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Maryline BeurgDidier Dulon
Jan 4, 2013·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Jihye LeeJ Troy Littleton
Sep 22, 2007·Proceedings of the National Academy of Sciences of the United States of America·Natalya KorogodRalf Schneggenburger
Jan 1, 2011·ISRN Neurology·Sumiko Mochida
Mar 30, 2013·Cerebral Cortex·Ayal LaviUri Ashery
Dec 28, 2006·The Journal of Cell Biology·Anton MaximovThomas C Südhof
Aug 19, 2014·Molecular and Cellular Neurosciences·Christian P MoritzEckhard Friauf
Jun 9, 2007·The Journal of Physiology·Nina VardjanRobert Zorec
Mar 29, 2011·Trends in Neurosciences·Olexiy KochubeyRalf Schneggenburger
Jun 22, 2010·Current Opinion in Cell Biology·Zhiping P Pang, Thomas C Südhof
Apr 10, 2009·Genesis : the Journal of Genetics and Development·Kimberly E MaceNoreen E Reist
Jun 8, 2007·The European Journal of Neuroscience·Shao-Ying HuaAylin Cimenser
Jan 24, 2009·Annals of the New York Academy of Sciences·Nina VardjanRobert Zorec
Jan 24, 2009·Annals of the New York Academy of Sciences·Nina Vardjan, Robert Zorec
Nov 26, 2008·The Journal of Comparative Neurology·Tobias MittelsteadtSusanne Schoch
Jun 19, 2012·The EMBO Journal·Jörg MalsamThomas H Söllner
Jun 22, 2010·The EMBO Journal·Jens P WeberJakob B Sørensen
Aug 8, 2015·Cellular and Molecular Life Sciences : CMLS·Ralf MohrmannDieter Bruns
Jan 27, 2015·Traffic·Devon C Crawford, Ege T Kavalali
Nov 26, 2009·The Journal of Comparative Neurology·Jianmin SuMichael A Fox

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