Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming
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Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming. / Papantoniou, Christos; Laugks, Ulrike; Betzin, Julia; Capitanio, Cristina; Ferrero, José Javier; Sánchez-Prieto, José; Schoch, Susanne; Brose, Nils; Baumeister, Wolfgang; Cooper, Benjamin H; Imig, Cordelia; Lučić, Vladan.
In: Science Advances, Vol. 9, No. 25, 2023.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming
AU - Papantoniou, Christos
AU - Laugks, Ulrike
AU - Betzin, Julia
AU - Capitanio, Cristina
AU - Ferrero, José Javier
AU - Sánchez-Prieto, José
AU - Schoch, Susanne
AU - Brose, Nils
AU - Baumeister, Wolfgang
AU - Cooper, Benjamin H
AU - Imig, Cordelia
AU - Lučić, Vladan
PY - 2023
Y1 - 2023
N2 - Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, and structural studies of purified systems were essential for our understanding of the function of the individual complexes involved, they cannot resolve how the actions of individual complexes integrate. We used cryo-electron tomography to simultaneously image multiple presynaptic protein complexes and lipids at molecular resolution in their native composition, conformation, and environment. Our detailed morphological characterization suggests that sequential synaptic vesicle states precede neurotransmitter release, where Munc13-comprising bridges localize vesicles <10 nanometers and soluble N-ethylmaleimide-sensitive factor attachment protein 25-comprising bridges <5 nanometers from the plasma membrane, the latter constituting a molecularly primed state. Munc13 activation supports the transition to the primed state via vesicle bridges to plasma membrane (tethers), while protein kinase C promotes the same transition by reducing vesicle interlinking. These findings exemplify a cellular function performed by an extended assembly comprising multiple molecularly diverse complexes.
AB - Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, and structural studies of purified systems were essential for our understanding of the function of the individual complexes involved, they cannot resolve how the actions of individual complexes integrate. We used cryo-electron tomography to simultaneously image multiple presynaptic protein complexes and lipids at molecular resolution in their native composition, conformation, and environment. Our detailed morphological characterization suggests that sequential synaptic vesicle states precede neurotransmitter release, where Munc13-comprising bridges localize vesicles <10 nanometers and soluble N-ethylmaleimide-sensitive factor attachment protein 25-comprising bridges <5 nanometers from the plasma membrane, the latter constituting a molecularly primed state. Munc13 activation supports the transition to the primed state via vesicle bridges to plasma membrane (tethers), while protein kinase C promotes the same transition by reducing vesicle interlinking. These findings exemplify a cellular function performed by an extended assembly comprising multiple molecularly diverse complexes.
U2 - 10.1126/sciadv.adf6222
DO - 10.1126/sciadv.adf6222
M3 - Journal article
C2 - 37343100
VL - 9
JO - Science advances
JF - Science advances
SN - 2375-2548
IS - 25
ER -
ID: 357270194