Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains

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


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / physiology*
  • Cell Adhesion Molecules / ultrastructure*
  • Cell Adhesion Molecules, Neuronal / physiology
  • Cell Adhesion Molecules, Neuronal / ultrastructure
  • Cells, Cultured
  • Hippocampus / physiology
  • Hippocampus / ultrastructure
  • Immunoglobulins / physiology*
  • Immunoglobulins / ultrastructure*
  • Male
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Mice, Transgenic
  • Microscopy, Immunoelectron
  • Neurons / physiology
  • Neurons / ultrastructure
  • Synapses / physiology*
  • Synapses / ultrastructure*


  • Cadm1 protein, mouse
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Cell Adhesion Molecules, Neuronal
  • Immunoglobulins