title: An activity-regulated microRNA, miR-188, controls dendritic plasticity and synaptic transmission by downregulating neuropilin-2.
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.
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors.forename: Kihwan
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Life Science, POSTECH, Pohang, Kyungbuk, 790-784, Korea.
authors.forename: Joung-Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Life Science, POSTECH, Pohang, Kyungbuk, 790-784, Korea.
authors.forename: Oh-Bin
authors.initials: OB
authors.lastname: Kwon
authors.affiliation: Department of Life Science, POSTECH, Pohang, Kyungbuk, 790-784, Korea.
authors.forename: Kyongman
authors.initials: K
authors.lastname: An
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors.forename: Junghwa
authors.initials: J
authors.lastname: Ryu
authors.affiliation: Henry Wellcome Laboratories for Integrative Neuroscience and Endocrinology (LINE), Faculty of Medicine and Dentistry, University of Bristol, Whitson Street, Bristol BS1 3NY, UK.|Department of Anatomy, University of Bristol, MRC Centre for Synaptic Plasticity, University Walk, Bristol BS8 1TD, UK.
authors.forename: Kwangwook
authors.initials: K
authors.lastname: Cho
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Korea.
authors.forename: Yoo-Hun
authors.initials: YH
authors.lastname: Suh
authors.affiliation: Department of Pharmacology and Biomedical Sciences, College of Medicine, Seoul National University, Seoul 110-799, Korea.|Seoul National University Bundang Hospital, Seoul National University, College of Medicine, Bundang-Gu, Sungnam, Kyungki, 463-707, Korea.
authors.forename: Hye-Sun
authors.initials: HS
authors.lastname: Kim
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001703:Biophysics; D002478:Cells, Cultured; D003712:Dendrites / Q000502:physiology*; D049229:Dendritic Spines / Q000378:metabolism; D015536:Down-Regulation / Q000235:genetics / Q000502:physiology*; D004558:Electric Stimulation / Q000379:methods; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D018756:GABA Antagonists / Q000494:pharmacology; D020869:Gene Expression Profiling; D005998:Glycine / Q000494:pharmacology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects / Q000235:genetics; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology*; D009474:Neurons / Q000166:cytology; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D018408:Patch-Clamp Techniques; D010852:Picrotoxin / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013331:Strychnine / Q000494:pharmacology; D013569:Synapses / Q000235:genetics / Q000502:physiology*; D009435:Synaptic Transmission / Q000235:genetics / Q000502:physiology*; D014162:Transfection
chemical_list: D018756:GABA Antagonists; D005998:Glycine; D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D035683:MicroRNAs; D039943:Neuropilin-2; D010852:Picrotoxin; D012333:RNA, Messenger; D013331:Strychnine; C413663:fluorescent protein 583