title: Preso, a novel PSD-95-interacting FERM and PDZ domain protein that regulates dendritic spine morphogenesis.
abstract: PSD-95 is an abundant postsynaptic density (PSD) protein involved in the formation and regulation of excitatory synapses and dendritic spines, but the underlying mechanisms are not comprehensively understood. Here we report a novel PSD-95-interacting protein Preso that regulates spine morphogenesis. Preso is mainly expressed in the brain and contains WW (domain with two conserved Trp residues), PDZ (PSD-95/Dlg/ZO-1), FERM (4.1, ezrin, radixin, and moesin), and C-terminal PDZ-binding domains. These domains associate with actin filaments, the Rac1/Cdc42 guanine nucleotide exchange factor betaPix, phosphatidylinositol-4,5-bisphosphate, and the postsynaptic scaffolding protein PSD-95, respectively. Preso overexpression increases the density of dendritic spines in a manner requiring WW, PDZ, FERM, and PDZ-binding domains. Conversely, knockdown or dominant-negative inhibition of Preso decreases spine density, excitatory synaptic transmission, and the spine level of filamentous actin. These results suggest that Preso positively regulates spine density through its interaction with the synaptic plasma membrane, actin filaments, PSD-95, and the betaPix-based Rac1 signaling pathway.
authors.affiliation: National Creative Research Initiative Center for Synaptogenesis and Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 305-701, Korea.
authors.forename: Hyun Woo
authors.initials: HW
authors.lastname: Lee
authors.forename: Jeonghoon
authors.initials: J
authors.lastname: Choi
authors.forename: Hyewon
authors.initials: H
authors.lastname: Shin
authors.forename: Karam
authors.initials: K
authors.lastname: Kim
authors.forename: Jinhee
authors.initials: J
authors.lastname: Yang
authors.forename: Moonseok
authors.initials: M
authors.lastname: Na
authors.forename: So Yoen
authors.initials: SY
authors.lastname: Choi
authors.forename: Gil Bu
authors.initials: GB
authors.lastname: Kang
authors.forename: Soo Hyun
authors.initials: SH
authors.lastname: Eom
authors.forename: Hyun
authors.initials: H
authors.lastname: Kim
authors.forename: Eunjoon
authors.initials: E
authors.lastname: Kim
mesh_terms: D008841:Actin Cytoskeleton / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D006224:Cricetinae; D003598:Cytoskeletal Proteins / Q000502:physiology*; D049229:Dendritic Spines / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D004622:Embryo, Mammalian; D015870:Gene Expression / Q000502:physiology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D051528:Guanylate Kinases; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008958:Models, Molecular; D009024:Morphogenesis / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000648:ultrastructure*; D054731:PDZ Domains / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism; D017434:Protein Structure, Tertiary; D051381:Rats; D009435:Synaptic Transmission / Q000235:genetics; D014162:Transfection; D020798:Two-Hybrid System Techniques
chemical_list: D003598:Cytoskeletal Proteins; D000076122:Disks Large Homolog 4 Protein; C501447:Dlg4 protein, mouse; C478965:EPB41L4B protein, human; C539678:FRMPD4 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; C079240:Mtap2 protein, mouse; D009419:Nerve Tissue Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; C485184:enhanced green fluorescent protein; C033652:postsynaptic density proteins; D049452:Green Fluorescent Proteins; D051528:Guanylate Kinases