Research article summary (published 12 Oct 2009):

Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking.

Full Abstract

The postsynaptic density (PSD) consists of a lattice-like array of interacting proteins that organizes and stabilizes receptors, ion channels, structural, and signaling proteins necessary for synaptic function. To study the stabilization of proteins within this structure and the contribution of these proteins to the integrity of the PSD, we tagged synaptic proteins with PAGFP (photoactivatable green fluorescent protein) and used combined two-photon laser-scanning microscopy and two-photon laser photoactivation to measure their rate of turnover in individual spines of rat CA1 pyramidal neurons. We find that PSD-95 is highly stable within the spine, more so than other PSD-associated proteins such as CaMKIIalpha, CaMKIIbeta, GluR2, and Stargazin. Analysis of a series of PSD-95 mutants revealed that distinct domains stabilize PSD-95 within the PSD and contribute to PSD formation. Stabilization of PSD-95 within the PSD requires N-terminal palmitoylation and protein interactions mediated by the first and second PDZ domains, whereas formation of a stable lattice of PSD-95 molecules within the PSD additionally requires the C-terminal SH3 domain. Furthermore, in a PDZ domain 1 and 2 dependent manner, activation of NMDA receptors with a chemical long-term depression protocol rapidly destabilizes PSD-95 and causes a subset of the PSD-95 molecules previously anchored in the spine to be released. Thus, through the analysis of rates of exchange of synaptic PSD-95, we determine separate domains of PSD-95 that play specific roles in establishing a stable postsynaptic lattice, in allowing proteins to enter this lattice, and in reorganizing this structure in response to plasticity-inducing stimuli.

Author information

Author/s: Sturgill, James F (JF); Steiner, Pascal (P); Czervionke, Brian L (BL); Sabatini, Bernardo L (BL);

Affiliation: Howard Hughes Medical Institute, Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA.

Grants: NS052707 (Agency:NINDS NIH HHS) ; (Agency:Howard Hughes Medical Institute)

Journal and publication information

Publication Type: In Vitro; Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't

Journal: The Journal of neuroscience : the official journal of the Society for Neuroscience (J Neurosci), published in United States. (Language: eng)

Reference: 2009-Oct; vol 29 (issue 41) : pp 12845-54

Dates: Created 2009/10/15; Completed 2009/10/30;

PMID: 19828799, status: MEDLINE (last retrieval date: 10/30/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Animals, Newborn Calcium-Calmodulin-Dependent Protein Kinase Kinase - genetics Dendritic Spines - drug effects; genetics; metabolism Excitatory Amino Acid Agonists - pharmacology Green Fluorescent Proteins - genetics Hippocampus - cytology Immunosuppressive Agents - pharmacology Intracellular Signaling Peptides and Proteins - genetics; metabolism Lipoylation - physiology Membrane Proteins - genetics; metabolism Mutation - genetics

N-Methylaspartate - pharmacology Organ Culture Techniques PDZ Domains - genetics; physiology Protein Structure, Tertiary - genetics; physiology Protein Transport - drug effects; genetics; physiology Rats Receptors, AMPA - genetics Signal Transduction - drug effects; genetics; physiology Synapses - drug effects; physiology Tacrolimus - pharmacology Time Factors Transfection - methods

Associated Chemicals: Dlgh4 protein, rat (0) ; Excitatory Amino Acid Agonists (0) ; Immunosuppressive Agents (0) ; Intracellular Signaling Peptides and Proteins (0) ; Membrane Proteins (0) ; Receptors, AMPA (0) ; glutamate receptor ionotropic, AMPA 2 (0) ; Tacrolimus (109581-93-3) ; Green Fluorescent Proteins (147336-22-9) ; N-Methylaspartate (6384-92-5) ; Calcium-Calmodulin-Dependent Protein Kinase Kinase (EC 2.7.11.17)

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