TY - JOUR
T1 - MicroRNA-134 activity in somatostatin interneurons regulates H-Ras localization by repressing the palmitoylation enzyme, DHHC9
AU - Chai, Sunghee
AU - Cambronne, Xiaolu A.
AU - Eichhorn, Stephen W.
AU - Goodman, Richard H.
PY - 2013/10/29
Y1 - 2013/10/29
N2 - 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.
AB - 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.
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U2 - 10.1073/pnas.1317528110
DO - 10.1073/pnas.1317528110
M3 - Article
C2 - 24127608
AN - SCOPUS:84887033963
SN - 0027-8424
VL - 110
SP - 17898
EP - 17903
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 44
ER -