Arc MRNA Docks Precisely at the Base of Individual Dendritic Spines Indicating the Existence of a Specialized Microdomain for Synapse-specific MRNA Translation

Overview

Journal J Comp Neurol

Specialty Neurology

Date 2012 Feb 22

PMID 22350812

Citations 34

Authors

Joseph L Dynes

Oswald Steward

Affiliations

Soon will be listed here.

Abstract

Arc (aka Arg 3.1) is induced by neural activity and learning experience. Arc mRNA is rapidly exported into dendrites where it localizes near activated synapses. By imaging green fluorescent protein (GFP)-tagged mRNA in living neurons in culture, we show that fusion transcripts containing the Arc 30'UTR (untranslated region) localize with remarkable precision in a microdomain at the base of dendritic spines. Transcripts with the Arc 30'UTR that encode a reporter protein rather than Arc show precise localization. Localization persists in the presence of translation inhibitors, indicating that localization does not require ongoing translation. Similarly, polyribosome complexes remained stably positioned at spine bases in brain tissue treated with the translation inhibitor (puromycin) that releases ribosomes from mRNA. Single particle tracking revealed that Arc mRNA particles positioned at spine bases exhibited highly constrained submicron movements. These observations imply the existence of a microdomain at the spine base where Arc mRNA docks in association with a previously unknown mRNA-binding structural element.

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References

Bassell G, Singer R, Kosik K . Association of poly(A) mRNA with microtubules in cultured neurons. Neuron. 1994; 12(3):571-82. DOI: 10.1016/0896-6273(94)90213-5. View

Steward O, Worley P . Selective targeting of newly synthesized Arc mRNA to active synapses requires NMDA receptor activation. Neuron. 2001; 30(1):227-40. DOI: 10.1016/s0896-6273(01)00275-6. View

Sage D, Neumann F, Hediger F, Gasser S, Unser M . Automatic tracking of individual fluorescence particles: application to the study of chromosome dynamics. IEEE Trans Image Process. 2005; 14(9):1372-83. DOI: 10.1109/tip.2005.852787. View

Dieterich D, Hodas J, Gouzer G, Shadrin I, Ngo J, Triller A . In situ visualization and dynamics of newly synthesized proteins in rat hippocampal neurons. Nat Neurosci. 2010; 13(7):897-905. PMC: 2920597. DOI: 10.1038/nn.2580. View

Link W, Konietzko U, Kauselmann G, Krug M, Schwanke B, Frey U . Somatodendritic expression of an immediate early gene is regulated by synaptic activity. Proc Natl Acad Sci U S A. 1995; 92(12):5734-8. PMC: 41771. DOI: 10.1073/pnas.92.12.5734. View

Guzowski J, Timlin J, Roysam B, McNaughton B, Worley P, Barnes C . Mapping behaviorally relevant neural circuits with immediate-early gene expression. Curr Opin Neurobiol. 2005; 15(5):599-606. DOI: 10.1016/j.conb.2005.08.018. View

Waung M, Pfeiffer B, Nosyreva E, Ronesi J, Huber K . Rapid translation of Arc/Arg3.1 selectively mediates mGluR-dependent LTD through persistent increases in AMPAR endocytosis rate. Neuron. 2008; 59(1):84-97. PMC: 2580055. DOI: 10.1016/j.neuron.2008.05.014. View

Kao D, Aldridge G, Weiler I, Greenough W . Altered mRNA transport, docking, and protein translation in neurons lacking fragile X mental retardation protein. Proc Natl Acad Sci U S A. 2010; 107(35):15601-6. PMC: 2932564. DOI: 10.1073/pnas.1010564107. View

Messaoudi E, Kanhema T, Soule J, Tiron A, Dagyte G, Silva B . Sustained Arc/Arg3.1 synthesis controls long-term potentiation consolidation through regulation of local actin polymerization in the dentate gyrus in vivo. J Neurosci. 2007; 27(39):10445-55. PMC: 6673172. DOI: 10.1523/JNEUROSCI.2883-07.2007. View

10.

Chowdhury S, Shepherd J, Okuno H, Lyford G, Petralia R, Plath N . Arc/Arg3.1 interacts with the endocytic machinery to regulate AMPA receptor trafficking. Neuron. 2006; 52(3):445-59. PMC: 1784006. DOI: 10.1016/j.neuron.2006.08.033. View

11.

Sanes J, Lichtman J . Can molecules explain long-term potentiation?. Nat Neurosci. 1999; 2(7):597-604. DOI: 10.1038/10154. View

12.

Aitken C, Petrov A, Puglisi J . Single ribosome dynamics and the mechanism of translation. Annu Rev Biophys. 2010; 39:491-513. DOI: 10.1146/annurev.biophys.093008.131427. View

13.

Dynes J, Steward O . Dynamics of bidirectional transport of Arc mRNA in neuronal dendrites. J Comp Neurol. 2006; 500(3):433-47. DOI: 10.1002/cne.21189. View

14.

Fusco D, Accornero N, Lavoie B, Shenoy S, Blanchard J, Singer R . Single mRNA molecules demonstrate probabilistic movement in living mammalian cells. Curr Biol. 2003; 13(2):161-167. PMC: 4764064. DOI: 10.1016/s0960-9822(02)01436-7. View

15.

Lyford G, Yamagata K, Kaufmann W, Barnes C, Sanders L, Copeland N . Arc, a growth factor and activity-regulated gene, encodes a novel cytoskeleton-associated protein that is enriched in neuronal dendrites. Neuron. 1995; 14(2):433-45. DOI: 10.1016/0896-6273(95)90299-6. View

16.

Kremerskothen J, Kindler S, Finger I, Veltel S, Barnekow A . Postsynaptic recruitment of Dendrin depends on both dendritic mRNA transport and synaptic anchoring. J Neurochem. 2006; 96(6):1659-66. DOI: 10.1111/j.1471-4159.2006.03679.x. View

17.

Guzowski J, McNaughton B, Barnes C, Worley P . Environment-specific expression of the immediate-early gene Arc in hippocampal neuronal ensembles. Nat Neurosci. 1999; 2(12):1120-4. DOI: 10.1038/16046. View

18.

Xie Y, Vessey J, Konecna A, Dahm R, Macchi P, Kiebler M . The GTP-binding protein Septin 7 is critical for dendrite branching and dendritic-spine morphology. Curr Biol. 2007; 17(20):1746-51. DOI: 10.1016/j.cub.2007.08.042. View

19.

Plath N, Ohana O, Dammermann B, Errington M, Schmitz D, Gross C . Arc/Arg3.1 is essential for the consolidation of synaptic plasticity and memories. Neuron. 2006; 52(3):437-44. DOI: 10.1016/j.neuron.2006.08.024. View

20.

Wang Z, Edwards J, Riley N, Provance Jr D, Karcher R, Li X . Myosin Vb mobilizes recycling endosomes and AMPA receptors for postsynaptic plasticity. Cell. 2008; 135(3):535-48. PMC: 2585749. DOI: 10.1016/j.cell.2008.09.057. View