MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9
Author(s)Chai, Sunghee; Cambronne, Xiaolu A.; Eichhorn, Stephen William; Goodman, Richard H.
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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.
DepartmentMassachusetts Institute of Technology. Department of Biology; Whitehead Institute for Biomedical Research
Proceedings of the National Academy of Sciences
National Academy of Sciences (U.S.)
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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