title: Topographic Mapping of the Synaptic Cleft into Adhesive Nanodomains.
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.
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Perez de Arce
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Nikolas
authors.initials: N
authors.lastname: Schrod
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Sarah W R
authors.initials: SWR
authors.lastname: Metzbower
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Edward
authors.initials: E
authors.lastname: Allgeyer
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Geoffrey K-W
authors.initials: GK
authors.lastname: Kong
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Ai-Hui
authors.initials: AH
authors.lastname: Tang
authors.affiliation: Department of Physiology, Universität Bonn Medical Faculty, 53115 Bonn, Germany.
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Krupp
authors.affiliation: Department of Physiology, Universität Bonn Medical Faculty, 53115 Bonn, Germany.
authors.forename: Valentin
authors.initials: V
authors.lastname: Stein
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Xinran
authors.initials: X
authors.lastname: Liu
authors.affiliation: Department of Cell Biology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Jörg
authors.initials: J
authors.lastname: Bewersdorf
authors.affiliation: Department of Physiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Blanpied
authors.affiliation: Department of Molecular Structural Biology, Max Planck Institute of Biochemistry, 82152 Martinsried, Germany.
authors.forename: Vladan
authors.initials: V
authors.lastname: Lucić
authors.affiliation: Department of Neuroscience, Tufts University School of Medicine, Boston, MA 02111, USA. Electronic address: thomas.biederer@tufts.edu.
authors.forename: Thomas
authors.initials: T
authors.lastname: Biederer
mesh_terms: D000818:Animals; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000502:physiology* / Q000648:ultrastructure*; D015816:Cell Adhesion Molecules, Neuronal / Q000502:physiology / Q000648:ultrastructure; D002478:Cells, Cultured; D006624:Hippocampus / Q000502:physiology / Q000648:ultrastructure; D007136:Immunoglobulins / Q000502:physiology* / Q000648:ultrastructure*; D008297:Male; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D009474:Neurons / Q000502:physiology / Q000648:ultrastructure; D013569:Synapses / Q000502:physiology* / Q000648:ultrastructure*
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins
keywords: CADM; EphB2; Nectin-like protein; SynCAM; adhesion; synapse; synaptic cleft