title: Actin polymerization and ERK phosphorylation are required for Arc/Arg3.1 mRNA targeting to activated synaptic sites on dendrites.
abstract: The mRNA for the immediate early gene Arc/Arg3.1 is induced by strong synaptic activation and is rapidly transported into dendrites, where it localizes at active synaptic sites. NMDA receptor activation is critical for mRNA localization at active synapses, but downstream events that mediate localization are not known. The patterns of synaptic activity that induce mRNA localization also trigger a dramatic polymerization of actin in the activated dendritic lamina and phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) throughout the postsynaptic cytoplasm. The local polymerization of actin in the activated dendritic lamina is of particular interest because it occurs in the same dendritic domains in which newly synthesized Arc/Arg3.1 mRNA localizes. Here, we explore the role of activity-induced alterations in the actin network and mitogen-activated protein (MAP) kinase activation in Arc/Arg3.1 mRNA localization. We show that actin polymerization induced by high-frequency stimulation is blocked by local inhibition of Rho kinase, and Arc/Arg3.1 mRNA localization is abrogated in the region of Rho kinase blockade. Local application of latrunculin B, which binds to actin monomers and inhibits actin polymerization, also blocked the targeting of Arc/Arg3.1 mRNA to activated synaptic sites. Local application of the MAP kinase kinase inhibitor U0126 (1,4-diamino-2,3-dicyano-1,4-bis[2-amino-phenylthio]butadiene) blocked ERK phosphorylation, and also blocked Arc/Arg3.1 mRNA localization. Our results indicate that the reorganization of the actin cytoskeletal network in conjunction with MAP kinase activation is required for targeting newly synthesized Arc/Arg3.1 mRNA to activated synaptic sites.
authors: Department of Anatomy and Neurobiology, Reeve-Irvine Research Center, Irvine, California 92697, USA.
authors: Fen
authors: F
authors: Huang
authors: Jennifer K
authors: JK
authors: Chotiner
authors: Oswald
authors: O
authors: Steward
mesh_terms: D000199:Actins / Q000378:metabolism*; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002070:Butadienes / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D003712:Dendrites / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D006624:Hippocampus / Q000166:cytology; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology / Q000528:radiation effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009474:Neurons / Q000166:cytology; D009570:Nitriles / Q000494:pharmacology; D019580:Perforant Pathway / Q000166:cytology / Q000502:physiology / Q000528:radiation effects; D010766:Phosphorylation / Q000187:drug effects / Q000528:radiation effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013569:Synapses / Q000187:drug effects / Q000378:metabolism* / Q000528:radiation effects; D053778:Thiazolidines / Q000494:pharmacology
chemical_list: D000199:Actins; D019086:Bridged Bicyclo Compounds, Heterocyclic; D002070:Butadienes; D003598:Cytoskeletal Proteins; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D009570:Nitriles; D012333:RNA, Messenger; D053778:Thiazolidines; C113580:U 0126; C092069:activity regulated cytoskeletal-associated protein; D048049:Extracellular Signal-Regulated MAP Kinases; C037068:latrunculin B
references: Science. 1999 Aug 6;285(5429):895-8
references: 10436159
references: J Neurosci. 1999 Sep 15;19(18):7834-45
references: 10479686
references: Nat Neurosci. 1999 Dec;2(12):1120-4
references: 10570490
references: J Neurosci. 2000 Jun 1;20(11):3993-4001
references: 10818134
references: J Neurosci. 2000 Jun 15;20(12):4563-72
references: 10844026
references: Curr Opin Neurobiol. 2000 Oct;10(5):582-6
references: 11084320
references: Results Probl Cell Differ. 2001;34:1-26
references: 11288670
references: Neuron. 2001 Apr;30(1):227-40
references: 11343657
references: Proc Natl Acad Sci U S A. 2001 Jun 19;98(13):7062-8
references: 11416188
references: J Neurosci. 2001 Aug 1;21(15):5484-93
references: 11466419
references: Annu Rev Cell Dev Biol. 2002;18:601-35
references: 12142283
references: Neuron. 2002 Aug 1;35(3):535-45
references: 12165474
references: Neuron. 2002 Sep 12;35(6):1019-27
references: 12354393
references: Neuron. 2003 May 8;38(3):447-60
references: 12741991
references: Eur J Neurosci. 2003 Jun;17(12):2679-89
references: 12823475
references: Curr Opin Cell Biol. 2004 Feb;16(1):80-5
references: 15037309
references: Neuroscience. 2004;125(1):7-11
references: 15051140
references: Mol Cell Neurosci. 2004 Jul;26(3):429-40
references: 15234347
references: Neuron. 2004 Aug 19;43(4):513-25
references: 15312650
references: Nat Neurosci. 2004 Oct;7(10):1104-12
references: 15361876
references: Neuron. 2004 Oct 14;44(2):321-34
references: 15473970
references: Neuron. 2004 Dec 2;44(5):749-57
references: 15572107
references: J Neurosci. 2005 Feb 23;25(8):2062-9
references: 15728846
references: J Neurobiol. 2005 Jul;64(1):47-57
references: 15884005
references: Curr Biol. 2005 May 10;15(9):869-73
references: 15886107
references: Neuron. 2005 Jul 7;47(1):85-100
references: 15996550
references: J Neurosci. 2005 Aug 3;25(31):7199-209
references: 16079402
references: Curr Opin Neurobiol. 2006 Feb;16(1):95-101
references: 16361095
references: J Cell Biol. 2006 Jan 30;172(3):453-67
references: 16449195
references: Proc Natl Acad Sci U S A. 2006 Apr 4;103(14):5579-84
references: 16567651
references: Neuron. 2006 Nov 9;52(3):403-7
references: 17088207
references: Neuron. 2006 Nov 9;52(3):437-44
references: 17088210
references: Neuron. 2006 Nov 9;52(3):445-59
references: 17088211
references: Neuron. 2006 Nov 9;52(3):461-74
references: 17088212
references: Neuron. 2006 Nov 9;52(3):475-84
references: 17088213
references: J Comp Neurol. 2007 Jan 20;500(3):433-47
references: 17120280
references: Curr Biol. 2006 Dec 5;16(23):2345-51
references: 17141617
references: Synapse. 1990;5(2):139-43
references: 2309158
references: Proc Natl Acad Sci U S A. 1982 Dec;79(23):7590-4
references: 6760199
references: Exp Neurol. 1981 Nov;74(2):621-7
references: 7297640
references: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5734-8
references: 7777577
references: Neuron. 1995 Feb;14(2):433-45
references: 7857651
references: Science. 1998 Jan 23;279(5350):509-14
references: 9438836
references: J Neurosci. 1998 Apr 1;18(7):2423-36
references: 9502803
references: Neuron. 1998 Oct;21(4):741-51
references: 9808461