Molecular Composition of the Postsynaptic Density

2/26/01


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Table of Contents

Synapse Specificity Through Molecular Compartmentalization

~50% of all Ca1 Spines have SER

Cerebellar Spine and SER compartments

Synapse Specificity through Local Protein Synthesis

Polyribosomes in spines If time also see website

Endocytosis in Spines

Actin not MT's = spine cytoskeleton

Spine Summary

Molecular Composition of the PSD

Postsynaptic Density

Molecular Organization

Illustration of the types of synaptic structures which can be purified from brain

Molecules identified by biochemical purification of the PSD

Glutamate Receptors and their associated proteins

Glutamate receptors and their associated proteins drawn to molecular scale fit easily in the PSD

Relative locations of Glutamate Receptors in the PSD based on Immunogold EM

NMDA receptor

NMDA receptor model

NMDA receptor - PSD-95 Complex

PSD-95

Function NR2 - PSD-95

Function NR2 - PSD-95

NR2 - PSD-95 - nNos

NR2 - PSD-95 - SynGAP

NR2 - PSD-95 - Fyn

NR2 - PSD-95 - GKAP to Shank

NR2 - PSD-95 - MAP1A and Cript

NR1 - gates the Ca channel through its interactions with cytoplasmic proteins

NR1 - actinin - F-actin

NR1 - CaM

NR1 - Yotaio - PP1, PKA

NR1 - F-actin Spectrin

AMPA receptor distribution in the PSD based on Immunogold EM

1 subunit of GluR3 "AMPA" glutamate receptor

Synaptic targeting of AMPA receptors

AMPA - GRIP/ABP

AMPA - GRIP/ABP

AMPA - PICK1

AMPA - NSF-SNAP

Metabotropic Glutamate Receptors in the PSD based on Immunogold EM

mGluR receptor structure

mGlu Receptor - Homer - IP3 receptor

mGluR1 - Homer - IP3

Structural "linkage" of SER at PSD edges

Structural "linkage" of SER at PSD edges

mGluR1 - Shank - NMDA complex

NMDA - Shank - Homer

Excitatory PSD Signaling Microdomains (SM)

Molecular Heterogeneity reflects Structural Diversity of Glutamatergic PSDs

Symmetric (inhibitory) and Asymmetric (excitatory) Synapses (Hippocampus)

Anchoring NX receptors at Inhibitory Synapses

Summary

Author: Harris