title: Prickle2 is localized in the postsynaptic density and interacts with PSD-95 and NMDA receptors in the brain.
abstract: The planar cell polarity (PCP) protein, Prickle (Pk), is conserved in invertebrates and vertebrates, and regulates cellular morphogenesis and movement. Vertebrate Pk consists of at least two family members, Pk1 and Pk2, both of which are expressed in the brain; however, their localization and function at synapses remain elusive. Here, we show that Pk2 is expressed mainly in the adult brain and is tightly associated with the postsynaptic density (PSD) fraction obtained by subcellular fractionation. In primary cultured rat hippocampal neurons, Pk2 is colocalized with PSD-95 and synaptophysin at synapses. Moreover, immunoelectron microcopy shows that Pk2 is localized at the PSD of asymmetric synapses in the hippocampal CA1 region. Biochemical assays identified that Pk2 forms a complex with PSD proteins including PSD-95 and NMDA receptor subunits via the direct binding to the C-terminal guanylate kinase domain of PSD-95. These results indicate that Pk2 is a novel PSD protein that interacts with PSD-95 and NMDA receptors through complex formations in the brain.
authors.affiliation: Department of Biochemistry, Faculty of Medicine/Graduate School of Medicine, University of Yamanashi, Chuo, Japan.
authors.forename: Yamato
authors.initials: Y
authors.lastname: Hida
authors.forename: Masahiro
authors.initials: M
authors.lastname: Fukaya
authors.forename: Akari
authors.initials: A
authors.lastname: Hagiwara
authors.forename: Maki
authors.initials: M
authors.lastname: Deguchi-Tawarada
authors.forename: Toshinori
authors.initials: T
authors.lastname: Yoshioka
authors.forename: Isao
authors.initials: I
authors.lastname: Kitajima
authors.forename: Eiji
authors.initials: E
authors.lastname: Inoue
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ohtsuka
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D002460:Cell Line; D003001:Cloning, Molecular; D000076122:Disks Large Homolog 4 Protein; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000737:chemistry* / Q000378:metabolism; D060588:LIM Domain Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry* / Q000172:deficiency / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D051381:Rats; D016194:Receptors, N-Methyl-D-Aspartate / Q000737:chemistry* / Q000378:metabolism; D013569:Synapses; D014018:Tissue Distribution
chemical_list: D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D008565:Membrane Proteins; C518732:Prickle2 protein, mouse; D016194:Receptors, N-Methyl-D-Aspartate