MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9

Sunghee Chai, Xiaolu A. Cambronne, Stephen W. Eichhorn, Richard H. Goodman

Research output: Contribution to journalArticle

31 Scopus citations

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 GABAA receptor antagonist, decreasedDHHC9 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.

Original languageEnglish (US)
Pages (from-to)17898-17903
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number44
DOIs
StatePublished - Oct 29 2013

ASJC Scopus subject areas

  • General

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