Table of Contents
Cell Adhesion at Synapses
Overview
Diversity of Cell Adhesion Junctions
2 liver Epithelial Cells
Intestinal Epithelial Cells
Model of Tight Junction
Experimental demonstration that tight junctions prevent passage of water-soluble substances
General Properties of Cell Adhesion Molecules (CAM)
Five Main Families of CAMs
Cadherin
Desmosome
Desmosomes between Epithelial Cells Note the various filaments
Integrin
Integrin based focal adhesions (green, Actin Stress Fibers red)
Integrin based focal adhesion
Summary of junctional and nonjunctional adhesion mechanisms
Cell-Cell Adhesion Junctions in CNS
Puctum Adherens are Small!
Puncta Adherens are frequent in the CNS Neuropil
Puncta Adherens at Synapses
DEFINITIONS
PA at synapse edge associated with pre and postsynaptic cytoskeletal elements and SER
Puncta Adherens surrounding a Vesicle free zone with indentation
Synaptic PA tend to be associated with dense bars of postsynaptic spine apparatus
Cell Adhesion Junctions at
Macular Synapses
Macular PSDs
Cell - Adhesion junctions at Perforated Synapses
Cell - Adhesion junctions at Perforated Synapses
Perforated PSDs
Synapses with PA and/or VFTZ
Association Between SER and Puncta Adhaerens
Puncta Adherens at other synapses
Symmetric Synapses and Punctum Adherens
Somato-dendritic synapse and puncta adherens
A mixed synapse
Schematic drawing of a typical cadherin molecule
Synapses Fig. 6-1b
Cadherin (green) at synaptic glomeruli (red - synaptophysin) cerebellar granule cell layer
Begin Here Wednesday -- left off at the edge of synapse
Summary
Hypothesis - Cadherin based Junctions (Calcium Dependent)
SYNAPSES - ASYMMETRIC CELL-CELL ADHESION JUNCTIONS
What is nature of adhesion in synaptic cleft?
EPTA - reveals Cleft Material
Bismuth Iodide reacting with basic amino residues reveals substructure of the cleft material
Comparison of synaptic membrane complexes
Functions of Cell Adhesion Molecules at Synapses
Classes of CAMs "in" Synapses
Cadherins and
Cadherin-related Neuronal Receptors
CNRs
CNRs appear to be synaptic not parasynaptic like Cadherins
(C-G) CNR1 synaptic junctions in the neocortex at 3 weeks.
Fyn - CNR1 binding
Regional similarities in CNR and fyn distributions throughout brain
Cell specificity of CNR expressions
Immunoglobulin Family
Schematic drawing of four forms of N-CAM
Polysialic acid site
General Ideas about Immunoglobulins
Neurexins - candidate synaptic CAM
Neurexins - prime candidates as synaptic CAM
Neurexin Domain Structures
LNS domain
Specificity of ?-Neurexin and ?-Neurexin ligand binding
?-Neurexin and CLs
Neurexophilins
Neurexophilins
2) Specificity of ?-Neurexin binding and the Neuroligin connection
Neuroligins
Neuroligin 1 monoclonal ABs
Neuroligin 1 monoclonal ABs
Synaptophysin monoclonal ABs
Structural Evidence for Neuroligin in synaptic cleft.
Model:
"Coating" Neurexin-Neuroligin Junction
Presynaptic Tripartite complex CASK, Mint 1, Veli
Presynaptic CASK
Presynaptic Mint 1
Presynaptic Function of the Tripartite Complex
Model:
"Coating" Neurexin-Neuroligin Junction
Model: Cytoplasmic Attachment proteins
"Coating" the Neuroligin
Neuroligin induces presynaptic differentiation
Linking Cell Adhesion to synaptic vesicles via Munc 18 and synaptotagmin
Heuristic value of the
Neurexin-Neuroligin Junction Model
Other candidate Synaptic CAMs
Other candidate Synaptic CAMs
Open Questions
Functions of Cell Adhesion Molecules at Synapses
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