Glutamate-induced RNA localization and translation in neurons

Young J. Yoon, Bin Wu, Adina R. Buxbaum, Sulagna Das, Albert Tsai, Brian P. English, Jonathan B. Grimm, Luke D. Lavis, Robert H. Singer

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Localization of mRNA is required for protein synthesis to occur within discrete intracellular compartments. Neurons represent an ideal system for studying the precision of mRNA trafficking because of their polarized structure and the need for synapsespecific targeting. To investigate this targeting, we derived a quantitative and analytical approach. Dendritic spines were stimulated by glutamate uncaging at a diffraction-limited spot, and the localization of single β-actin mRNAs was measured in space and time. Localization required NMDA receptor activity, a dynamic actin cytoskeleton, and the transacting RNA-binding protein, Zipcodebinding protein 1 (ZBP1). The ability of the mRNA to direct newly synthesized proteins to the site of localization was evaluated using a Halo-actin reporter so that RNA and protein were detected simultaneously. Newly synthesized Halo-actin was enriched at the site of stimulation, required NMDA receptor activity, and localized preferentially at the periphery of spines. This work demonstrates that synaptic activity can induce mRNA localization and local translation of β-actin where the new actin participates in stabilizing the expanding synapse in dendritic spines.

Original languageEnglish (US)
Pages (from-to)E6877-E6886
JournalProceedings of the National Academy of Sciences of the United States of America
Volume113
Issue number44
DOIs
StatePublished - Nov 1 2016

Fingerprint

Actins
Glutamic Acid
RNA
Neurons
Messenger RNA
Dendritic Spines
N-Methyl-D-Aspartate Receptors
Proteins
RNA-Binding Proteins
Actin Cytoskeleton
Synapses
Spine

Keywords

  • Glutamate uncaging
  • HaloTag
  • RNA localization
  • Single molecule
  • β-actin

ASJC Scopus subject areas

  • General

Cite this

Glutamate-induced RNA localization and translation in neurons. / Yoon, Young J.; Wu, Bin; Buxbaum, Adina R.; Das, Sulagna; Tsai, Albert; English, Brian P.; Grimm, Jonathan B.; Lavis, Luke D.; Singer, Robert H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 113, No. 44, 01.11.2016, p. E6877-E6886.

Research output: Contribution to journalArticle

Yoon, Young J. ; Wu, Bin ; Buxbaum, Adina R. ; Das, Sulagna ; Tsai, Albert ; English, Brian P. ; Grimm, Jonathan B. ; Lavis, Luke D. ; Singer, Robert H. / Glutamate-induced RNA localization and translation in neurons. In: Proceedings of the National Academy of Sciences of the United States of America. 2016 ; Vol. 113, No. 44. pp. E6877-E6886.
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