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Neuron. 2015 Dec 16;88(6):1165-1172. doi: 10.1016/j.neuron.2015.11.011.

Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains.

Author information

1
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
2
Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
3
Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
4
Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
5
Department of Physiology, Universität Bonn Medical Faculty, 53115 Bonn, Germany.
6
Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA. Electronic address: thomas.biederer@tufts.edu.

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.

KEYWORDS:

CADM; EphB2; Nectin-like protein; SynCAM; adhesion; synapse; synaptic cleft

PMID:
26687224
PMCID:
PMC4687029
DOI:
10.1016/j.neuron.2015.11.011
[Indexed for MEDLINE]
Free PMC Article

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