Local palmitoylation cycles define activity-regulated postsynaptic subdomains. Academic Article uri icon

Overview

abstract

  • 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.

publication date

  • July 8, 2013

Research

keywords

  • Dendritic Spines
  • Lipoylation
  • Neurons
  • Post-Synaptic Density

Identity

PubMed Central ID

  • PMC3704990

Scopus Document Identifier

  • 84880590079

Digital Object Identifier (DOI)

  • 10.1186/1472-6750-10-59

PubMed ID

  • 23836932

Additional Document Info

volume

  • 202

issue

  • 1