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J. Neurosci., Apr 18 2012, 32 (16) | https://doi.org/10.1523/JNEUROSCI.6471-11.2012 An activity-regulated microRNA, miR-188, controls dendritic plasticity and synaptic transmission by downregulating neuropilin-2

Kihwan Lee ^1,†, Joung-Hun Kim ^2,†, Oh-Bin Kwon ^2,†, Kyongman An ², Junghwa Ryu ¹, Kwangwook Cho ^3,4, Yoo-Hun Suh ^1,*, Hye-Sun Kim ^1,5,*

¹Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Korea
²Department of Life Science, Pohang University of Science and Technology, Pohang, Kyungbuk 790-784, Korea
³Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology, Faculty of Medicine and Dentistry, University of Bristol, Bristol BS1 3NY, United Kingdom
⁴Department of Anatomy, University of Bristol, Medical Research Council Centre for Synaptic Plasticity, Bristol BS8 1TD, United Kingdom
⁵Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Bundang-Gu, Sungnam, Kyungki 463-707, Korea

^†These authors contributed equally

*Corresponding authors: correspondence to Yoo-Hun Suh or Hye-Sun Kim

Abstract

MicroRNAs (miRNAs) have recently come to be viewed as critical players that modulate a number of cellular features in various biological systems including the mature CNS by exerting regulatory control over the stability and translation of mRNAs. Despite considerable evidence for the regulatory functions of miRNAs, the identities of the miRNA species that are involved in the regulation of synaptic transmission and plasticity and the mechanisms by which these miRNAs exert functional roles remain largely unknown. In the present study, the expression of microRNA-188 (miR-188) was found to be upregulated by the induction of long-term potentiation (LTP). The protein level of neuropilin-2 (Nrp-2), one of the possible molecular targets for miR-188, was decreased during LTP induction. We also confirmed that the luciferase activity of the 3'-UTR of Nrp-2 was diminished by treatment with a miR-188 oligonucleotide but not with a scrambled miRNA oligonucleotide. Nrp-2 serves as a receptor for semaphorin 3F, which is a negative regulator of spine development and synaptic structure. In addition, miR-188 specifically rescued the reduction in dendritic spine density induced by Nrp-2 expression in hippocampal neurons from rat primary culture. Furthermore, miR-188 counteracted the decrease in the miniature EPSC frequency induced by Nrp-2 expression in hippocampal neurons from rat primary culture. These findings suggest that miR-188 serves to fine-tune synaptic plasticity by regulating Nrp-2 expression.

논문정보

형식Research article
게재일2012년 04월 (BRIC 등록일 2025-06-09)
연구진국내(교신)+국외 연구진
분야 생명과학 > 신경생물학
피인용횟수120회 이상 인용된 논문

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