MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9
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Chai-2013-MicroRNA-134 activit.pdf
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Author(s)
Chai, Sunghee
Cambronne, Xiaolu A.
Eichhorn, Stephen William
Goodman, Richard H.
Date Issued
October 2013
Journal
Proceedings of the National Academy of Sciences
Publisher
National Academy of Sciences (U.S.)
Citation
Chai, S., X. A. Cambronne, S. W. Eichhorn, and R. H. Goodman. “MicroRNA-134 Activity in Somatostatin Interneurons Regulates H-Ras Localization by Repressing the Palmitoylation Enzyme, DHHC9.” Proceedings of the National Academy of Sciences 110, no. 44 (October 14, 2013): 17898–17903.
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Final published version
Abstract
MicroRNA-134 (miR-134) serves as a widely accepted model for microRNA function in synaptic plasticity. In this model, synaptic activity stimulates miR-134 expression, which then regulates dendrite growth and spine formation. By using a ratiometric microRNA sensor, we found, unexpectedly, that miR-134 activity in cortical neurons was restricted to interneurons. Using an assay designed to trap microRNA–mRNA complexes, we determined that miR-134 interacted directly with the mRNA encoding the palmitoylation enzyme, DHHC9. This enzyme is known to palmitoylate H-Ras, a modification required for proper membrane trafficking. Treatment with bicuculline, a GABA[subscript A] receptor antagonist, decreased DHHC9 expression in somatostatin-positive interneurons and membrane localization of an H-Ras reporter in a manner that depended on miR-134. Thus, although miR-134 has been proposed to affect all types of neurons, we showed that functionally active miR-134 is produced in only a selected population of neurons where it influences the expression of targets, such as DHHC9, that regulate membrane targeting of critical signaling molecules.
MIT Department
Massachusetts Institute of Technology. Department of Biology
Whitehead Institute for Biomedical Research
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Article is available under a Creative Commons license; see publisher’s site for details.
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DOI of Published Version
https://doi.org/10.1073/pnas.1317528110
