title: Lateral assembly of the immunoglobulin protein SynCAM 1 controls its adhesive function and instructs synapse formation.
abstract: Synapses are specialized adhesion sites between neurons that are connected by protein complexes spanning the synaptic cleft. These trans-synaptic interactions can organize synapse formation, but their macromolecular properties and effects on synaptic morphology remain incompletely understood. Here, we demonstrate that the synaptic cell adhesion molecule SynCAM 1 self-assembles laterally via its extracellular, membrane-proximal immunoglobulin (Ig) domains 2 and 3. This cis oligomerization generates SynCAM oligomers with increased adhesive capacity and instructs the interactions of this molecule across the nascent and mature synaptic cleft. In immature neurons, cis assembly promotes the adhesive clustering of SynCAM 1 at new axo-dendritic contacts. Interfering with the lateral self-assembly of SynCAM 1 in differentiating neurons strongly impairs its synaptogenic activity. At later stages, the lateral oligomerization of SynCAM 1 restricts synaptic size, indicating that this adhesion molecule contributes to the structural organization of synapses. These results support that lateral interactions assemble SynCAM complexes within the synaptic cleft to promote synapse induction and modulate their structure. These findings provide novel insights into synapse development and the adhesive mechanisms of Ig superfamily members.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, CT, USA.
authors.forename: Adam I
authors.initials: AI
authors.lastname: Fogel
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Stagi
authors.forename: Karen
authors.initials: K
authors.lastname: Perez de Arce
authors.forename: Thomas
authors.initials: T
authors.lastname: Biederer
mesh_terms: D000818:Animals; D019556:COS Cells; D002448:Cell Adhesion / Q000502:physiology; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules / Q000737:chemistry / Q000378:metabolism; D015816:Cell Adhesion Molecules, Neuronal / Q000737:chemistry / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D018920:Coculture Techniques; D031541:Fluorescence Resonance Energy Transfer; D057809:HEK293 Cells; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D007136:Immunoglobulins / Q000737:chemistry / Q000378:metabolism; D007150:Immunohistochemistry; D051379:Mice; D016501:Neurites / Q000378:metabolism*; D020836:Protein Structure, Quaternary / Q000502:physiology*; D013569:Synapses / Q000378:metabolism*
chemical_list: C498598:Cadm1 protein, mouse; D000075982:Cell Adhesion Molecule-1; D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D007136:Immunoglobulins