Morphofunctional changes at the active zone during synaptic vesicle exocytosis
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Morphofunctional changes at the active zone during synaptic vesicle exocytosis. / Radecke, Julika; Seeger, Raphaela; Kádková, Anna; Laugks, Ulrike; Khosrozadeh, Amin; Goldie, Kenneth N.; Lučić, Vladan; Sørensen, Jakob B.; Zuber, Benoît.
In: EMBO Reports, Vol. 24, No. 5, e55719, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Morphofunctional changes at the active zone during synaptic vesicle exocytosis
AU - Radecke, Julika
AU - Seeger, Raphaela
AU - Kádková, Anna
AU - Laugks, Ulrike
AU - Khosrozadeh, Amin
AU - Goldie, Kenneth N.
AU - Lučić, Vladan
AU - Sørensen, Jakob B.
AU - Zuber, Benoît
N1 - Publisher Copyright: © 2023 The Authors. Published under the terms of the CC BY 4.0 license.
PY - 2023
Y1 - 2023
N2 - 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.
AB - 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.
KW - cryo-electron tomography
KW - SNARE
KW - synapse
KW - synaptic vesicles
U2 - 10.15252/embr.202255719
DO - 10.15252/embr.202255719
M3 - Journal article
C2 - 36876590
AN - SCOPUS:85149628075
VL - 24
JO - E M B O Reports
JF - E M B O Reports
SN - 1469-221X
IS - 5
M1 - e55719
ER -
ID: 340103362