Structural organization and function of mouse photoreceptor ribbon synapses involve the immunoglobulin protein synaptic cell adhesion molecule 1

J Comp Neurol. 2014 Mar;522(4):900-20. doi: 10.1002/cne.23452.

Abstract

Adhesive interactions in the retina instruct the developmental specification of inner retinal layers. However, potential roles of adhesion in the development and function of photoreceptor synapses remain incompletely understood. This contrasts with our understanding of synapse development in the CNS, which can be guided by select adhesion molecules such as the Synaptic Cell Adhesion Molecule 1 (SynCAM 1/CADM1/nectin-like 2 protein). This immunoglobulin superfamily protein modulates the development and plasticity of classical excitatory synapses. We show here by immunoelectron microscopy and immunoblotting that SynCAM 1 is expressed on mouse rod photoreceptors and their terminals in the outer nuclear and plexiform layers in a developmentally regulated manner. Expression of SynCAM 1 on rods is low in early postnatal stages (P3-P7) but increases after eye opening (P14). In support of functional roles in the photoreceptors, electroretinogram recordings demonstrate impaired responses to light stimulation in SynCAM 1 knockout (KO) mice. In addition, the structural integrity of synapses in the OPL requires SynCAM 1. Quantitative ultrastructural analysis of SynCAM 1 KO retina measured fewer fully assembled, triadic rod ribbon synapses. Furthermore, rod synapse ribbons are shortened in KO mice, and protein levels of Ribeye, a major structural component of ribbons, are reduced in SynCAM 1 KO retina. Together, our results implicate SynCAM 1 in the synaptic organization of the rod visual pathway and provide evidence for novel roles of synaptic adhesion in the structural and functional integrity of ribbon synapses.

Keywords: CADM; SynCAM; electroretinography; nectin-like protein; retina; ribbon synapse; rod.

Publication types

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

MeSH terms

  • Alcohol Oxidoreductases
  • Analysis of Variance
  • Animals
  • Animals, Newborn
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules / genetics
  • Cell Adhesion Molecules / metabolism*
  • Cell Adhesion Molecules / ultrastructure
  • Co-Repressor Proteins
  • DNA-Binding Proteins / metabolism
  • Electroretinography
  • Female
  • Gene Expression Regulation, Developmental / genetics
  • Immunoglobulins / genetics
  • Immunoglobulins / metabolism*
  • Immunoglobulins / ultrastructure
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Microscopy, Immunoelectron
  • Nerve Tissue Proteins / metabolism
  • Phosphoproteins / metabolism
  • Receptors, Metabotropic Glutamate / metabolism
  • Retina / cytology*
  • Retina / growth & development*
  • Retinal Rod Photoreceptor Cells / ultrastructure*
  • Synapses / metabolism*
  • Synapses / ultrastructure
  • Vesicular Glutamate Transport Protein 1 / metabolism

Substances

  • Cadm1 protein, mouse
  • Cell Adhesion Molecule-1
  • Cell Adhesion Molecules
  • Co-Repressor Proteins
  • DNA-Binding Proteins
  • Immunoglobulins
  • Nerve Tissue Proteins
  • Phosphoproteins
  • Receptors, Metabotropic Glutamate
  • Slc17a7 protein, mouse
  • Vesicular Glutamate Transport Protein 1
  • metabotropic glutamate receptor 6
  • Alcohol Oxidoreductases
  • Ctbp2 protein, mouse