Centre Broca Nouvelle-Aquitaine
Title : Architecture of trans-synaptic assemblies at the single nanometer scale.
Neurotransmitter release is mediated by a complex and highly regulated molecular machinery. We imaged isolated synapses by cryo-electron tomography (cryo-ET), a method that utilizes faithful sample preservation and direct 3D imaging of fully hydrated, unlabeled biological material at 2-4 nanometer resolution. The computational procedures for template-free detection and classification in cryo-tomograms that we developed allowed us to quantitatively analyze the spatial organization and inter-relation of synaptic complexes. We showed that tripartite trans-synaptic assemblies (subcolumns) link synaptic vesicles to postsynaptic ionotropic glutamate receptors, and established that a particular displacement between the interacting complexes characterizes subcolumns. Furthermore, we obtained de novo average structures of ionotropic glutamate receptors in their physiological composition, embedded in plasma membrane. In a separate set experiments, we found that Munc13 and SNAP25, proteins known to be essential for synaptic vesicle priming for release and fusion, control the location of synaptic vesicles at a single nanometer precision by tethering them to the plasma membrane, resulting in two stable primed vesicle states. Furthermore, these two proteins, together with protein kinase C, control the transition between the two primed states by coordinated reorganization of both tethers and molecular bridges (connectors) that interlink vesicles. Together, our data supports the hypothesis that synaptic transmission is carried by precisely aligned trans-synaptic units that are organized in large molecular assemblies of variable architecture.
Martinez-Sanchez wt al., 2021. Trans-synaptic assemblies link synaptic vesicles and neuroreceptors. Science advances
Martinez-Sanchez et al., 2020. Template-free detection and classification of membrane-
bound complexes in cryo-electron tomograms. Nature methods 17:209–216.
Zuber, B., and V. Lucic, 2019. Molecular architecture of the presynaptic terminal. Current opinion
in structural biology 54:129–138.
Organized by Bordeaux Neurocampus, NBA and Bordeaux Neurocampus Graduate Program
Project Group Leader
Research Department Molecular Structural Biology
Max Planck Institute of Biochemistry
Martinsried, Munich, Germany
Share a pizza with the speaker
Ph.D. students are invited to a networking event with the guest speaker around some pizzas.
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