title: Postsynaptic PDLIM5/Enigma Homolog binds SPAR and causes dendritic spine shrinkage.
abstract: Dendritic spine morphology is thought to play important roles in synaptic development and plasticity, and morphological derangements in spines are correlated with several neurological disorders. Here, we identified an interaction between Spine-Associated RapGAP (SPAR), a postsynaptic protein that reorganizes actin cytoskeleton and drives dendritic spine head growth, and PDLIM5/Enigma Homolog (ENH), a PDZ-LIM (postsynaptic density-95/Discs large/zona occludens 1-Lin11/Isl-1/Mec3) family member. PDLIM5 has been implicated in susceptibility to bipolar disorder, major depression, and schizophrenia, but its function in neurological disease is poorly understood. We show that PDLIM5 is present in the postsynaptic density, where it promotes decreased dendritic spine head size and longer, filopodia-like morphology. Conversely, RNA interference against PDLIM5 or loss of PDLIM5 interaction with SPAR caused increased spine head diameter. Furthermore, PKC activation promoted delivery of PDLIM5 into dendritic spines and increased its spine colocalization with SPAR. These data reveal new postsynaptic functions for PDLIM5 in shrinkage of dendritic spines that may be relevant to its association with psychiatric illness.
authors.affiliation: Department of Pharmacology, Georgetown University Medical Center, Washington, DC 20057-1464, USA.
authors.forename: Scott
authors.initials: S
authors.lastname: Herrick
authors.forename: Danielle M
authors.initials: DM
authors.lastname: Evers
authors.forename: Ji-Yun
authors.initials: JY
authors.lastname: Lee
authors.forename: Noriko
authors.initials: N
authors.lastname: Udagawa
authors.forename: Daniel T S
authors.initials: DT
authors.lastname: Pak
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000378:metabolism; D019556:COS Cells; D002273:Carcinogens / Q000494:pharmacology; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D049229:Dendritic Spines / Q000187:drug effects / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D020690:GTPase-Activating Proteins / Q000235:genetics / Q000378:metabolism*; D005968:Glutamate Decarboxylase / Q000378:metabolism; D049452:Green Fluorescent Proteins / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D047468:Immunoprecipitation / Q000379:methods; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D018613:Microscopy, Confocal / Q000379:methods; D009154:Mutation / Q000502:physiology; D009388:Neostigmine / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000648:ultrastructure*; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D034622:RNA Interference / Q000502:physiology; D051381:Rats; D013569:Synapses / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000494:pharmacology; D014162:Transfection / Q000379:methods
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002273:Carcinogens; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D020690:GTPase-Activating Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D020033:Protein Isoforms; C479629:Sipa1l1 protein, rat; D049452:Green Fluorescent Proteins; D009388:Neostigmine; C020922:4-O-methyl-12-O-tetradecanoylphorbol 13-acetate; D005968:Glutamate Decarboxylase; D013755:Tetradecanoylphorbol Acetate