title: MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9.
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.
authors.affiliation: Vollum Institute, Oregon Health and Science University, Portland, OR 97239.
authors.forename: Sunghee
authors.initials: S
authors.lastname: Chai
authors.forename: Xiaolu A
authors.initials: XA
authors.lastname: Cambronne
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Eichhorn
authors.forename: Richard H
authors.initials: RH
authors.lastname: Goodman
mesh_terms: D000217:Acyltransferases / Q000378:metabolism*; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D015153:Blotting, Western; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D007091:Image Processing, Computer-Assisted; D007150:Immunohistochemistry; D007395:Interneurons / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D018613:Microscopy, Confocal; D016296:Mutagenesis; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D019864:Somatostatin-Secreting Cells / Q000378:metabolism*; D013569:Synapses / Q000378:metabolism*
chemical_list: C581995:MIRN134 microRNA, rat; D035683:MicroRNAs; D012333:RNA, Messenger; D000217:Acyltransferases; C585476:Zdhhc9 protein, rat; D001640:Bicuculline
keywords: RISC-trap; palmitoyltransferase