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| Title | Munc13- and SNAP25-dependent molecular bridges play a key role in synaptic vesicle priming. |
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| Journal, issue, pages | Sci Adv, Vol. 9, Issue 25, Page eadf6222, Year 2023 |
| Publish date | Jun 23, 2023 |
 Authors | Christos Papantoniou / Ulrike Laugks / Julia Betzin / Cristina Capitanio / José Javier Ferrero / José Sánchez-Prieto / Susanne Schoch / Nils Brose / Wolfgang Baumeister / Benjamin H Cooper / Cordelia Imig / Vladan Lučić /    |
| PubMed Abstract | Synaptic vesicle tethering, priming, and neurotransmitter release require a coordinated action of multiple protein complexes. While physiological experiments, interaction data, and structural studies ...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 -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. |
 External links | Sci Adv / PubMed:37343100 / PubMed Central |
| Methods | EM (tomography) |
| Structure data |  EMDB-16083: Munc13-SNAP25 cryo-ET dataset, synapse tomo WT 108 (id: m13_ctrl_108)  EMDB-16084: Munc13-SNAP25 cryo-ET dataset, synapse tomo Munc13 DHet 115 (id: m13_dhet_115)  EMDB-16085: Munc13-SNAP25 cryo-ET dataset, synapse tomo Munc13 DKO 102 (id: m13_dko_102) |
| Source |
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Mus musculus (house mouse)