Local palmitoylation cycles define activity-regulated postsynaptic subdomains

Distinct PSD-95 clusters are primary landmarks of postsynaptic densities (PSDs), which are specialized membrane regions for synapses. However, the mechanism that defines the locations of PSD-95 clusters and whether or how they are reorganized inside individual dendritic spines remains controversial....

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Published in:The Journal of cell biology 2013-07, Vol.202 (1), p.145-161
Main Authors: Fukata, Yuko, Dimitrov, Ariane, Boncompain, Gaelle, Vielemeyer, Ole, Perez, Franck, Fukata, Masaki
Format: Article
Language:English
Subjects:
Animals
Cells
Cercopithecus aethiops
COS Cells
Dendritic Spines - drug effects
Dendritic Spines - metabolism
Disks Large Homolog 4 Protein
Fluorescent Dyes - metabolism
Green Fluorescent Proteins - metabolism
Guanylate Kinases - metabolism
HEK293 Cells
Hippocampus - metabolism
Humans
Lipoylation
Membrane Proteins - metabolism
Membranes
Mice
Neuronal Plasticity
Neurons - metabolism
Palmitates - pharmacology
Plasma
Post-Synaptic Density - metabolism
Rats
Sensitivity and Specificity
Structure-Activity Relationship
Synaptic Transmission
Transfection
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Summary:Distinct PSD-95 clusters are primary landmarks of postsynaptic densities (PSDs), which are specialized membrane regions for synapses. However, the mechanism that defines the locations of PSD-95 clusters and whether or how they are reorganized inside individual dendritic spines remains controversial. Because palmitoylation regulates PSD-95 membrane targeting, we combined a conformation-specific recombinant antibody against palmitoylated PSD-95 with live-cell super-resolution imaging and discovered subsynaptic nanodomains composed of palmitoylated PSD-95 that serve as elementary units of the PSD. PSD-95 in nanodomains underwent continuous de/repalmitoylation cycles driven by local palmitoylating activity, ensuring the maintenance of compartmentalized PSD-95 clusters within individual spines. Plasma membrane targeting of DHHC2 palmitoyltransferase rapidly recruited PSD-95 to the plasma membrane and proved essential for postsynaptic nanodomain formation. Furthermore, changes in synaptic activity rapidly reorganized PSD-95 nano-architecture through plasma membrane-inserted DHHC2. Thus, the first genetically encoded antibody sensitive to palmitoylation reveals an instructive role of local palmitoylation machinery in creating activity-responsive PSD-95 nanodomains, contributing to the PSD (re)organization.
ISSN:0021-9525
1540-8140
DOI:10.1083/jcb.201302071