title: Local palmitoylation cycles define activity-regulated postsynaptic subdomains.
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.
authors.affiliation: Division of Membrane Physiology, Department of Cell Physiology, National Institute for Physiological Sciences, Okazaki, Aichi 444-8787, Japan.
authors.forename: Yuko
authors.initials: Y
authors.lastname: Fukata
authors.forename: Ariane
authors.initials: A
authors.lastname: Dimitrov
authors.forename: Gaelle
authors.initials: G
authors.lastname: Boncompain
authors.forename: Ole
authors.initials: O
authors.lastname: Vielemeyer
authors.forename: Franck
authors.initials: F
authors.lastname: Perez
authors.forename: Masaki
authors.initials: M
authors.lastname: Fukata
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000187:drug effects / Q000378:metabolism*; D000076122:Disks Large Homolog 4 Protein; D005456:Fluorescent Dyes / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051528:Guanylate Kinases / Q000378:metabolism; D057809:HEK293 Cells; D006624:Hippocampus / Q000378:metabolism; D006801:Humans; D054878:Lipoylation; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D009473:Neuronal Plasticity; D009474:Neurons / Q000378:metabolism*; D010168:Palmitates / Q000494:pharmacology; D057907:Post-Synaptic Density / Q000378:metabolism*; D051381:Rats; D012680:Sensitivity and Specificity; D013329:Structure-Activity Relationship; D009435:Synaptic Transmission; D014162:Transfection
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; D005456:Fluorescent Dyes; D008565:Membrane Proteins; D010168:Palmitates; D049452:Green Fluorescent Proteins; C022776:2-bromopalmitate; D051528:Guanylate Kinases