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Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains

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Schrod,  Nikolas
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Kong,  Geoffrey K. - W.
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Lucic,  Vladan
Baumeister, Wolfgang / Molecular Structural Biology, Max Planck Institute of Biochemistry, Max Planck Society;

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Citation

de Arce, K. P., Schrod, N., Metzbower, S. W. R., Allgeyer, E., Kong, G.-K.-.-W., Tang, A.-H., et al. (2015). Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains. NEURON, 88(6), 1165-1172. doi:10.1016/j.neuron.2015.11.011.


Cite as: https://hdl.handle.net/11858/00-001M-0000-0029-AD0A-8
Abstract
The cleft is an integral part of synapses, yet its macromolecular organization remains unclear. We show here that the cleft of excitatory synapses exhibits a distinct density profile as measured by cryoelectron tomography (cryo-ET). Aiming for molecular insights, we analyzed the synapse-organizing proteins Synaptic Cell Adhesion Molecule 1 (SynCAM 1) and EphB2. Cryo-ET of SynCAM 1 knockout and overexpressor synapses showed that this immunoglobulin protein shapes the cleft's edge. SynCAM 1 delineates the postsynaptic perimeter as determined by immunoelectron microscopy and super-resolution imaging. In contrast, the EphB2 receptor tyrosine kinase is enriched deeper within the postsynaptic area. Unexpectedly, SynCAM 1 can form ensembles proximal to postsynaptic densities, and synapses containing these ensembles were larger. Postsynaptic SynCAM 1 surface puncta were not static but became enlarged after a long-term depression paradigm. These results support that the synaptic cleft is organized on a nanoscale into sub-compartments marked by distinct trans-synaptic complexes.