biostudies-literatureChai SNIMH NIH HHSNINDS NIH HHS17898-903https://www.ebi.ac.uk/biostudies/studies/S-EPMC3816481biostudies-literatureUnknown110(44)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 mProceedings of the National Academy of Sciences of the United States of AmericaMicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9.PMC3816481NS097317NS076094MH099099P30 NS069305F32 NS076094R01 MH099099Eichhorn SWChai SCambronne XAGoodman RHfalseMicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9.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 m2013-01-01T00:00:00Z2013 Oct2025-04-04T12:47:25.371Z2019-03-27T01:18:04ZS-EPMC38164812412760810.1073/pnas.1317528110