title: Control of synaptic connection by glutamate receptor delta2 in the adult cerebellum.
abstract: Precise topological matching of presynaptic and postsynaptic specializations is essential for efficient synaptic transmission. Furthermore, synaptic connections are subjected to rearrangements throughout life. Here we examined the role of glutamate receptor (GluR) delta2 in the adult brain by inducible and cerebellar Purkinje cell (PC)-specific gene targeting under the pure C57BL/6 genetic background. Concomitant with the decrease of postsynaptic GluRdelta2 proteins, presynaptic active zones shrank progressively and postsynaptic density (PSD) expanded, resulting in mismatching between presynaptic and postsynaptic specializations at parallel fiber-PC synapses. Furthermore, GluRdelta2 and PSD-93 proteins were concentrated at the contacted portion of mismatched synapses, whereas AMPA receptors were distributed in both the contacted and dissociated portions. When GluRdelta2 proteins were diminished, PC spines lost their synaptic contacts. We thus identified postsynaptic GluRdelta2 as a key regulator of the presynaptic active zone and PSD organization at parallel fiber-PC synapses in the adult brain.
authors.affiliation: Department of Molecular Neurobiology and Pharmacology, Graduate School of Medicine, University of Tokyo, and Solution Oriented Research for Science and Technology, Japan Science and Technology Agency, Tokyo 113-0033, Japan.
authors.forename: Tomonori
authors.initials: T
authors.lastname: Takeuchi
authors.forename: Taisuke
authors.initials: T
authors.lastname: Miyazaki
authors.forename: Masahiko
authors.initials: M
authors.lastname: Watanabe
authors.forename: Hisashi
authors.initials: H
authors.lastname: Mori
authors.forename: Kenji
authors.initials: K
authors.lastname: Sakimura
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Mishina
mesh_terms: D000818:Animals; D002531:Cerebellum / Q000378:metabolism* / Q000648:ultrastructure; D003712:Dendrites / Q000648:ultrastructure; D005260:Female; D018390:Gene Targeting; D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016253:Microscopy, Immunoelectron; D015735:Mifepristone / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000032:analysis; D009473:Neuronal Plasticity / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology / Q000648:ultrastructure; D011689:Purkinje Cells / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D018091:Receptors, AMPA / Q000032:analysis; D017470:Receptors, Glutamate / Q000235:genetics / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000502:physiology; D011995:Recombination, Genetic / Q000187:drug effects; D013569:Synapses / Q000648:ultrastructure; D013997:Time Factors
chemical_list: D051528:Guanylate Kinases; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D015735:Mifepristone; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D018091:Receptors, AMPA; D017470:Receptors, Glutamate; D011993:Recombinant Fusion Proteins; C107913:glutamate receptor delta 2; C104723:glutamate receptor ionotropic, AMPA 3; C033652:postsynaptic density proteins; C501445:Dlg2 protein, mouse; C104722:glutamate receptor ionotropic, AMPA 2
references.citation: Science. 1999 Mar 19;283(5409):1923-7
references.pmid: 10082466
references.citation: J Neurosci. 1999 May 15;19(10):3926-34
references.pmid: 10234023
references.citation: Nature. 1999 May 6;399(6731):66-70
references.pmid: 10331391
references.citation: J Neurosci. 1999 Dec 1;19(23):10318-23
references.pmid: 10575029
references.citation: Nat Neurosci. 2000 Mar;3(3):238-44
references.pmid: 10700255
references.citation: J Biol Chem. 2000 May 26;275(21):16167-73
references.pmid: 10748123
references.citation: Annu Rev Neurosci. 2000;23:649-711
references.pmid: 10845078
references.citation: J Comp Neurol. 2000 Oct 30;426(4):572-86
references.pmid: 11027400
references.citation: Cell. 2000 Dec 8;103(6):945-56
references.pmid: 11136979
references.citation: Biochem Biophys Res Commun. 2001 Mar;281(5):1134-40
references.pmid: 11243853
references.citation: Eur J Neurosci. 2001 Mar;13(6):1249-53
references.pmid: 11285022
references.citation: J Neurosci. 2001 May 1;21(9):3085-91
references.pmid: 11312293
references.citation: Mol Cell Neurosci. 2001 May;17(5):921-30
references.pmid: 11358488
references.citation: Nat Neurosci. 2001 Jun;4(6):597-604
references.pmid: 11369940
references.citation: Eur J Neurosci. 2001 Jun;13(11):2025-36
references.pmid: 11422443
references.citation: Neuroscience. 2001;105(2):443-55
references.pmid: 11672610
references.citation: Nat Rev Neurosci. 2001 Dec;2(12):880-8
references.pmid: 11733795
references.citation: J Neurosci. 2001 Dec 15;21(24):9701-12
references.pmid: 11739579
references.citation: J Neurosci. 2002 Feb 1;22(3):803-14
references.pmid: 11826110
references.citation: Biochem Biophys Res Commun. 2002 May 10;293(3):953-7
references.pmid: 12051751
references.citation: J Neurosci. 2002 Oct 1;22(19):8487-503
references.pmid: 12351723
references.citation: Annu Rev Neurosci. 2003;26:485-508
references.pmid: 12626697
references.citation: Nature. 2003 Aug 7;424(6949):677-81
references.pmid: 12904794
references.citation: Biochem Biophys Res Commun. 1992 Mar 16;183(2):886-92
references.pmid: 1372507
references.citation: Neuron. 2003 Oct 9;40(2):243-64
references.pmid: 14556707
references.citation: J Neurosci. 2003 Oct 15;23(28):9367-73
references.pmid: 14561864
references.citation: Nat Rev Neurosci. 2004 Jan;5(1):45-54
references.pmid: 14708003
references.citation: Nature. 2004 Jan 29;427(6973):451-7
references.pmid: 14749834
references.citation: J Neurosci. 2004 Feb 18;24(7):1734-43
references.pmid: 14973254
references.citation: Eur J Neurosci. 2004 Apr;19(8):2017-29
references.pmid: 15090029
references.citation: Mol Cell Neurosci. 2004 Jun;26(2):330-41
references.pmid: 15207857
references.citation: Nat Rev Neurosci. 2004 Oct;5(10):771-81
references.pmid: 15378037
references.citation: Science. 1990 Aug 3;249(4968):556-60
references.pmid: 2166337
references.citation: Science. 1990 Apr 13;248(4952):183-8
references.pmid: 2183351
references.citation: Science. 1966 Dec 23;154(3756):1575-7
references.pmid: 5924927
references.citation: Biochem Biophys Res Commun. 1993 Dec 30;197(3):1267-76
references.pmid: 7506541
references.citation: Cell. 1995 Apr 21;81(2):245-52
references.pmid: 7736576
references.citation: J Comp Neurol. 1993 Dec 15;338(3):377-90
references.pmid: 8113446
references.citation: Int Immunol. 1993 Aug;5(8):957-64
references.pmid: 8398989
references.citation: FEBS Lett. 1993 Jan 11;315(3):318-22
references.pmid: 8422924
references.citation: Cell. 1993 Jan;72 Suppl:77-98
references.pmid: 8428376
references.citation: Annu Rev Physiol. 1993;55:397-426
references.pmid: 8466181
references.citation: Brain Res Dev Brain Res. 1996 Apr 30;92(2):147-55
references.pmid: 8738121
references.citation: Neuroreport. 1995 Dec 29;7(1):189-92
references.pmid: 8742448
references.citation: Cell. 1996 Dec 27;87(7):1327-38
references.pmid: 8980238
references.citation: J Neurosci. 1997 Jan 15;17(2):834-42
references.pmid: 8987804
references.citation: Neuron. 1997 Sep;19(3):519-30
references.pmid: 9331345
references.citation: Brain Res. 1997 Oct 10;771(1):1-13
references.pmid: 9383002
references.citation: J Neurosci. 1997 Dec 15;17(24):9613-23
references.pmid: 9391016
references.citation: J Comp Neurol. 1998 May 25;395(1):112-20
references.pmid: 9590549
references.citation: J Neurosci. 1998 Jul 15;18(14):5517-28
references.pmid: 9651232
references.citation: Eur J Neurosci. 1998 Feb;10(2):478-87
references.pmid: 9749710