Morphofunctional changes at the active zone during synaptic vesicle exocytosis.
SNARE
cryo-electron tomography
synapse
synaptic vesicles
Journal
EMBO reports
ISSN: 1469-3178
Titre abrégé: EMBO Rep
Pays: England
ID NLM: 100963049
Informations de publication
Date de publication:
04 05 2023
04 05 2023
Historique:
revised:
30
01
2023
received:
06
07
2022
accepted:
16
02
2023
medline:
5
5
2023
pubmed:
7
3
2023
entrez:
6
3
2023
Statut:
ppublish
Résumé
Synaptic vesicle (SV) fusion with the plasma membrane (PM) proceeds through intermediate steps that remain poorly resolved. The effect of persistent high or low exocytosis activity on intermediate steps remains unknown. Using spray-mixing plunge-freezing cryo-electron tomography we observe events following synaptic stimulation at nanometer resolution in near-native samples. Our data suggest that during the stage that immediately follows stimulation, termed early fusion, PM and SV membrane curvature changes to establish a point contact. The next stage-late fusion-shows fusion pore opening and SV collapse. During early fusion, proximal tethered SVs form additional tethers with the PM and increase the inter-SV connector number. In the late-fusion stage, PM-proximal SVs lose their interconnections, allowing them to move toward the PM. Two SNAP-25 mutations, one arresting and one disinhibiting spontaneous release, cause connector loss. The disinhibiting mutation causes loss of membrane-proximal multiple-tethered SVs. Overall, tether formation and connector dissolution are triggered by stimulation and respond to spontaneous fusion rate manipulation. These morphological observations likely correspond to SV transition from one functional pool to another.
Identifiants
pubmed: 36876590
doi: 10.15252/embr.202255719
pmc: PMC10157379
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e55719Informations de copyright
© 2023 The Authors. Published under the terms of the CC BY 4.0 license.
Références
J Cell Biol. 1989 May;108(5):1863-72
pubmed: 2497106
Curr Opin Neurobiol. 2017 Apr;43:63-70
pubmed: 28103533
Curr Biol. 2004 Feb 3;14(3):173-83
pubmed: 14761649
Cell Rep. 2019 Feb 26;26(9):2340-2352.e5
pubmed: 30811985
Nat Protoc. 2008;3(11):1718-28
pubmed: 18927557
J Struct Biol. 1996 Jan-Feb;116(1):71-6
pubmed: 8742726
Chembiochem. 2011 May 2;12(7):1049-55
pubmed: 21433241
Neuron. 2014 Oct 22;84(2):416-31
pubmed: 25374362
Ultramicroscopy. 1994 Dec;56(4):241-52
pubmed: 7831735
J Neurosci. 2007 Aug 29;27(35):9380-91
pubmed: 17728451
Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15079-84
pubmed: 23980146
Nat Struct Mol Biol. 2011 Jun 05;18(7):805-12
pubmed: 21642968
Front Synaptic Neurosci. 2010 Oct 05;2:135
pubmed: 21423521
Nat Methods. 2007 Mar;4(3):215-7
pubmed: 17277781
J Mol Biol. 2012 Oct 5;422(5):617-634
pubmed: 22841691
J Biol Chem. 2005 Nov 4;280(44):37278-88
pubmed: 16148008
Elife. 2020 Feb 20;9:
pubmed: 32077852
Traffic. 2008 Sep;9(9):1414-24
pubmed: 18445120
J Struct Biol. 2017 Feb;197(2):73-82
pubmed: 27444390
Curr Opin Struct Biol. 2019 Feb;54:129-138
pubmed: 30925443
J Neurosci. 2017 Nov 1;37(44):10597-10610
pubmed: 28954868
Biophys J. 2019 Jul 23;117(2):247-257
pubmed: 31301806
EMBO Rep. 2023 May 4;24(5):e55719
pubmed: 36876590
Cell. 2010 Mar 5;140(5):601-5
pubmed: 20211126
J Vis Exp. 2014 Feb 12;(84):e50783
pubmed: 24561719
Neuron. 2013 Oct 30;80(3):675-90
pubmed: 24183019
J Physiol. 2001 Mar 1;531(Pt 2):481-93
pubmed: 11230520
J Cell Biol. 2010 Feb 8;188(3):401-13
pubmed: 20142423
EMBO Rep. 2014 Mar;15(3):308-14
pubmed: 24493260
Science. 2010 Oct 22;330(6003):502-5
pubmed: 20847232
PLoS Comput Biol. 2019 Jun 24;15(6):e1007128
pubmed: 31233491
Nat Neurosci. 2002 Jan;5(1):19-26
pubmed: 11753414
Proc Natl Acad Sci U S A. 2016 Aug 2;113(31):E4548-57
pubmed: 27432975
J Struct Biol. 2014 May;186(2):302-7
pubmed: 24680783
J Neurosci. 2012 Mar 21;32(12):3969-80
pubmed: 22442064
J Cell Biol. 1989 Jan;108(1):111-26
pubmed: 2536030
Neuron. 1996 Jun;16(6):1197-207
pubmed: 8663996
Nature. 2018 Feb 8;554(7691):260-263
pubmed: 29420480
Annu Rev Biophys. 2015;44:339-67
pubmed: 26098518
J Mol Biol. 2005 Mar 4;346(4):967-89
pubmed: 15701510
Elife. 2016 Aug 19;5:
pubmed: 27542193
J Struct Biol. 2007 Nov;160(2):135-45
pubmed: 17884579
Neuron. 2016 Aug 17;91(4):808-823
pubmed: 27537485
Neuron. 2015 Sep 23;87(6):1131-1142
pubmed: 26402599
Nat Methods. 2013 Jun;10(6):584-90
pubmed: 23644547
J Struct Biol. 2005 Oct;152(1):36-51
pubmed: 16182563
Trends Neurosci. 2021 Jul;44(7):579-592
pubmed: 34049722
Nature. 1998 Sep 24;395(6700):347-53
pubmed: 9759724
J Cell Biol. 1981 Mar;88(3):564-80
pubmed: 6260814
J Cell Biol. 2010 Jan 11;188(1):145-56
pubmed: 20065095
J Biol Chem. 2009 Nov 13;284(46):32158-66
pubmed: 19759010
Science. 2012 Sep 14;337(6100):1340-3
pubmed: 22903523
J Struct Biol. 2016 Dec;196(3):503-514
pubmed: 27742578
Protein Sci. 2018 Aug;27(8):1364-1391
pubmed: 29893445
J Neurosci. 2007 Jun 27;27(26):6868-77
pubmed: 17596435
J Cell Biol. 1979 May;81(2):275-300
pubmed: 38256
Nat Neurosci. 2020 Nov;23(11):1329-1338
pubmed: 32989294
Neuron. 1988 May;1(3):201-9
pubmed: 3152289
Science. 2012 Mar 16;335(6074):1355-9
pubmed: 22422984
Nat Neurosci. 2001 Dec;4(12):1187-93
pubmed: 11685225
EMBO J. 2010 Aug 4;29(15):2477-90
pubmed: 20562829
Front Syst Neurosci. 2019 Jul 17;13:30
pubmed: 31379524
J Cell Biol. 2013 May 27;201(5):725-40
pubmed: 23712261
Proc Natl Acad Sci U S A. 2018 Dec 11;115(50):12751-12756
pubmed: 30482862
Annu Rev Biophys. 2022 May 9;51:377-408
pubmed: 35167762
J Neurosci. 2005 Apr 13;25(15):3842-50
pubmed: 15829636
Brain Res. 1988 Feb 16;441(1-2):72-80
pubmed: 2834007
Biophys J. 2005 Sep;89(3):2091-102
pubmed: 15980175
EMBO J. 2006 Mar 8;25(5):955-66
pubmed: 16498411