title: FMRP-Mediated Axonal Delivery of miR-181d Regulates Axon Elongation by Locally Targeting Map1b and Calm1.
abstract: Subcellular targeting and local translation of mRNAs are critical for axon development. However, the precise local control of mRNA translation requires investigation. We report that the Fmr1-encoded protein, FMRP-mediated axonal delivery of miR-181d negatively regulates axon elongation by locally targeting the transcripts of MAP1B (Map1b) and calmodulin (Calm1) in primary sensory neurons. miR-181d affected the local synthesis of MAP1B and calmodulin in axons. FMRP was associated with miR-181d, Map1b, and Calm1. Both FMRP deficiency in Fmr1(I304N) mice and Fmr1 knockdown impeded the axonal delivery of miR-181d, Map1b, and Calm1 and reduced the protein levels of MAP1B and calmodulin in axons. Furthermore, nerve growth factor (NGF) induced Map1b and Calm1 release from FMRP and miR-181d-repressing granules, thereby promoting axon elongation. Both miR-181d overexpression and FMRP knockdown impaired NGF-induced axon elongation. Our study reveals a mechanism for the local regulation of translation by miR-181d and FMRP during axon development.
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Pan
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Manyi
authors.initials: M
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wang
authors.affiliation: National Center of Nanoscience and Technology, Beijing 100190, China.
authors.forename: Wen-Wen
authors.initials: WW
authors.lastname: Liu
authors.affiliation: National Center of Nanoscience and Technology, Beijing 100190, China.
authors.forename: Nuoxin
authors.initials: N
authors.lastname: Wang
authors.affiliation: National Center of Nanoscience and Technology, Beijing 100190, China.
authors.forename: Xing-Yu
authors.initials: XY
authors.lastname: Jiang
authors.affiliation: Institute of Neuroscience and State Key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Cell Biology, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China; School of Life Science and Technology, ShanghaiTech University, Shanghai 200031, China. Electronic address: baolan@sibcb.ac.cn.
authors.forename: Lan
authors.initials: L
authors.lastname: Bao
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism*; D002147:Calmodulin / Q000235:genetics* / Q000378:metabolism; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D008869:Microtubule-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
chemical_list: D002147:Calmodulin; D051860:Fragile X Messenger Ribonucleoprotein 1; D035683:MicroRNAs; D008869:Microtubule-Associated Proteins; C000595843:Calm1 protein, mouse; C497684:Fmr1 protein, mouse; C555937:MIRN191 microRNA, mouse; C085284:microtubule-associated protein 1B