title: Modulation of mGluR-dependent MAP1B translation and AMPA receptor endocytosis by microRNA miR-146a-5p.
abstract: The translation of dendritic microtubule-associated protein 1B (MAP1B) is exaggerated upon group I mGluR activation leading to AMPA receptor (AMPAR) endocytosis and consequent long-term depression. However, the mechanisms of regulation of MAP1B protein synthesis in the mature dendrites remain unclear. Here we have identified miR-146a-5p that targets the 3' UTR of MAP1B mRNA and represses its translation. Inhibition of the endogenous miR-146a-5p in mouse cultured hippocampal neurons triggers an increase of the dendritic MAP1B protein as well as the internalization of AMPARs, resulting in a decline in synaptic transmission. Conversely, enforced expression of miR-146a-5p inhibits MAP1B translation and attenuates group I mGluR-induced AMPAR endocytosis. Moreover, siRNA-mediated knockdown of MAP1B recovers the impairment of synaptic transmission caused by inhibition of miR-146a-5p. These results reveal that miR-146a-5p modulates the synaptic plasticity via repression of MAP1B protein synthesis.
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei 112, Taiwan, Republic of China.
authors.forename: Ying-Lin
authors.initials: YL
authors.lastname: Chen
authors.forename: Che-Kun James
authors.initials: CK
authors.lastname: Shen
mesh_terms: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D002478:Cells, Cultured; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism; D004558:Electric Stimulation; D004622:Embryo, Mammalian; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006624:Hippocampus / Q000166:cytology; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D018408:Patch-Clamp Techniques; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D018091:Receptors, AMPA / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
chemical_list: D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D018691:Excitatory Amino Acid Antagonists; D008734:Methoxyhydroxyphenylglycol; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D018091:Receptors, AMPA; D014633:Valine; C534190:Mirn146 microRNA, mouse; C085284:microtubule-associated protein 1B; C056639:2-amino-5-phosphopentanoic acid; C010117:3,4-dihydroxyphenylglycol