MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9
- 14 October 2013
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 110 (44), 17898-17903
- https://doi.org/10.1073/pnas.1317528110
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, 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.Keywords
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