title: Localization and local translation of Arc/Arg3.1 mRNA at synapses: some observations and paradoxes.
abstract: Arc is a unique immediate early gene whose expression is induced as synapses are being modified during learning. The uniqueness comes from the fact that newly synthesized Arc mRNA is rapidly transported throughout dendrites where it localizes near synapses that were recently activated. Here, we summarize aspects of Arc mRNA translation in dendrites in vivo, focusing especially on features of its expression that are paradoxical or that donot fit in with current models of how Arc protein operates. Findings from in vivo studies that donot quite fit include: (1) Following induction of LTP in vivo, Arc mRNA and protein localize near active synapses, but are also distributed throughout dendrites. In contrast, Arc mRNA localizes selectively near active synapses when stimulation is continued as Arc mRNA is transported into dendrites; (2) Strong induction of Arc expression as a result of a seizure does not lead to a rundown of synaptic efficacy in vivo as would be predicted by the hypothesis that high levels of Arc cause glutamate receptor endocytosis and LTD. (3) Arc protein is synthesized in the perinuclear cytoplasm rapidly after transcriptional activation, indicating that at least a pool of Arc mRNA is not translationally repressed to allow for dendritic delivery; (4) Increases in Arc mRNA in dendrites are not paralleled by increases in levels of exon junction complex (EJC) proteins. These results of studies of mRNA trafficking in neurons in vivo provide a new perspective on the possible roles of Arc in activity-dependent synaptic modifications.
authors: Reeve-Irvine Research Center, University of California Irvine Irvine, CA, USA ; Department of Anatomy and Neurobiology, University of California Irvine Irvine, CA, USA ; Department of Neurobiology and Behavior, University of California Irvine Irvine, CA, USA ; Center for the Neurobiology of Learning and Memory, University of California Irvine Irvine, CA, USA.
authors: Oswald
authors: O
authors: Steward
authors: Reeve-Irvine Research Center, University of California Irvine Irvine, CA, USA ; Department of Anatomy and Neurobiology, University of California Irvine Irvine, CA, USA.
authors: Shannon
authors: S
authors: Farris
authors: Reeve-Irvine Research Center, University of California Irvine Irvine, CA, USA ; Department of Neurobiology and Behavior, University of California Irvine Irvine, CA, USA.
authors: Patricia S
authors: PS
authors: Pirbhoy
authors: Laboratory of Molecular Neuro-Oncology, The Rockefeller University New York, NY, USA.
authors: Jennifer
authors: J
authors: Darnell
authors: Laboratory of Molecular Neuro-Oncology, The Rockefeller University New York, NY, USA.
authors: Sarah J Van
authors: SJ
authors: Driesche
keywords: Arc/Arg3.1; LTP; dendrite; dendritic mRNA; dendritic spines; immediate early genes; protein synthesis; synaptic plasticity
references: Neuron. 2006 Nov 9;52(3):461-74
references: 17088212
references: Neuron. 1995 Feb;14(2):433-45
references: 7857651
references: Neuron. 2006 Nov 9;52(3):437-44
references: 17088210
references: Neuron. 2013 Oct 2;80(1):72-9
references: 24094104
references: Cell. 2007 Jul 13;130(1):179-91
references: 17632064
references: Neuron. 2006 Nov 9;52(3):445-59
references: 17088211
references: Nat Neurosci. 2013 Jul;16(7):874-83
references: 23749147
references: J Neurosci. 2006 Jul 5;26(27):7143-6
references: 16822969
references: J Comp Neurol. 2007 Jan 20;500(3):433-47
references: 17120280
references: J Comp Neurol. 2012 Oct 1;520(14):3105-19
references: 22350812
references: Nat Rev Neurosci. 2005 May;6(5):376-87
references: 15861180
references: Genes Dev. 2005 Apr 15;19(8):903-18
references: 15805463
references: Neuron. 2003 Oct 9;40(2):347-59
references: 14556713
references: Neuron. 2001 Apr;30(1):227-40
references: 11343657
references: Nat Neurosci. 2006 Jul;9(7):887-95
references: 16732277
references: Neuron. 2008 Jul 10;59(1):84-97
references: 18614031
references: Proc Natl Acad Sci U S A. 1995 Jun 6;92(12):5734-8
references: 7777577
references: Neuron. 2006 Nov 9;52(3):475-84
references: 17088213
references: Neuron. 2008 Jul 10;59(1):70-83
references: 18614030
references: Hippocampus. 2002;12(5):609-36
references: 12440577
references: J Neurosci. 2006 Jul 5;26(27):7139-42
references: 16822968
references: J Neurosci. 2000 Jun 1;20(11):3993-4001
references: 10818134
references: J Neurosci. 1998 Jan 1;18(1):26-35
references: 9412483
references: Exp Brain Res. 2010 Jan;200(2):125-40
references: 19690847
references: Curr Opin Neurobiol. 2002 Apr;12(2):211-6
references: 12015239
references: Nat Neurosci. 1999 Dec;2(12):1120-4
references: 10570490
references: Science. 2001 Nov 2;294(5544):1030-8
references: 11691980
references: Neuron. 1998 Oct;21(4):741-51
references: 9808461
references: Cell. 2012 May 11;149(4):886-98
references: 22579289
references: J Neurosci. 2006 Jul 5;26(27):7147-50
references: 16822970
references: J Neurosci. 2007 Sep 26;27(39):10445-55
references: 17898216
references: Hum Mol Genet. 2009 Sep 1;18(17):3164-77
references: 19487368
references: EMBO J. 2011 Aug 31;30(17):3540-52
references: 21878995
references: J Neurosci. 2009 Jan 28;29(4):898-906
references: 19176799
references: J Neurosci. 2007 Aug 22;27(34):9054-67
references: 17715342
references: J Neurosci. 2014 Mar 26;34(13):4481-93
references: 24671994