期刊
JOURNAL OF CELL BIOLOGY
卷 202, 期 1, 页码 145-161出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1083/jcb.201302071
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资金
- Human Frontier Science Program (HFSP) [RGY0059-06]
- HFSP [CDA0015-07, LT000029/2010-L]
- Ministry of Education, Culture, Sports, Science, and Technology (MEXT) [23110520]
- Association Francaise contre les Myopathies
- Centre National de la Recherche Scientifique (CNRS)
- Institut Curie
- Agence Nationale de la Recherche [ANR-09-BLAN-0290]
- Institut National du Cancer [2009-1-PL BIO-12-IC-1]
- Funding Program for Next Generation World-Leading Researchers [LS123]
- Agence Nationale de la Recherche (ANR) [ANR-09-BLAN-0290] Funding Source: Agence Nationale de la Recherche (ANR)
- Grants-in-Aid for Scientific Research [25110733] Funding Source: KAKEN
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.
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