title: miR-9 and miR-124 synergistically affect regulation of dendritic branching via the AKT/GSK3β pathway by targeting Rap2a.
abstract: A single microRNA (miRNA) can regulate expression of multiple proteins, and expression of an individual protein may be controlled by numerous miRNAs. This regulatory pattern strongly suggests that synergistic effects of miRNAs play critical roles in regulating biological processes. miR-9 and miR-124, two of the most abundant miRNAs in the mammalian nervous system, have important functions in neuronal development. In this study, we identified the small GTP-binding protein Rap2a as a common target of both miR-9 and miR-124. miR-9 and miR-124 together, but neither miRNA alone, strongly suppressed Rap2a, thereby promoting neuronal differentiation of neural stem cells (NSCs) and dendritic branching of differentiated neurons. Rap2a also diminished the dendritic complexity of mature neurons by decreasing the levels of pAKT and pGSK3β. Our results reveal a novel pathway in which miR-9 and miR-124 synergistically repress expression of Rap2a to sustain homeostatic dendritic complexity during neuronal development and maturation.
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Xue
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Caiyong
authors.initials: C
authors.lastname: Yu
authors.affiliation: Oral and maxillofacial surgery, Stomatology Hospital of Xi'an Jiaotong University, 710004, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ling
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Kun
authors.initials: K
authors.lastname: Zhang
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Chao
authors.initials: C
authors.lastname: Fang
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Fangfang
authors.initials: F
authors.lastname: Liu
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Ganlan
authors.initials: G
authors.lastname: Bian
authors.affiliation: Cardiff Institute of Tissue Engineering &Repair, School of Dentistry, Cardiff University, Cardiff, CF14 4XY, UK.
authors.forename: Bing
authors.initials: B
authors.lastname: Song
authors.affiliation: Department of Immunology, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Angang
authors.initials: A
authors.lastname: Yang
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Gong
authors.initials: G
authors.lastname: Ju
authors.affiliation: Institute of Neurosciences, the Fourth Military Medical University, Xi'an 710032, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wang
mesh_terms: D020413:3' Untranslated Regions / Q000235:genetics; D000818:Animals; D003712:Dendrites / Q000648:ultrastructure; D005786:Gene Expression Regulation / Q000235:genetics*; D000071679:Glycogen Synthase Kinase 3 beta / Q000502:physiology; D057809:HEK293 Cells; D006706:Homeostasis; D006801:Humans; D051379:Mice; D035683:MicroRNAs / Q000235:genetics*; D058953:Neural Stem Cells / Q000166:cytology; D055495:Neurogenesis / Q000235:genetics*; D009474:Neurons / Q000648:ultrastructure; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D020668:rap GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology
chemical_list: D020413:3' Untranslated Regions; C551804:MIRN9 microRNA, mouse; D035683:MicroRNAs; C540079:Mirn124 microRNA, mouse; D011993:Recombinant Fusion Proteins; D000071679:Glycogen Synthase Kinase 3 beta; D051057:Proto-Oncogene Proteins c-akt; C492137:Rap2a protein, mouse; D020668:rap GTP-Binding Proteins