title: Importin-7 mediates memory consolidation through regulation of nuclear translocation of training-activated MAPK in Drosophila.
abstract: Translocation of signaling molecules, MAPK in particular, from the cytosol to nucleus represents a universal key element in initiating the gene program that determines memory consolidation. Translocation mechanisms and their behavioral impact, however, remain to be determined. Here, we report that a highly conserved nuclear transporter, Drosophila importin-7 (DIM-7), regulates import of training-activated MAPK for consolidation of long-term memory (LTM). We show that silencing DIM-7 functions results in impaired LTM, whereas overexpression of DIM-7 enhances LTM. This DIM-7-dependent regulation of LTM is confined to a consolidation time window and in mushroom body neurons. Image data show that bidirectional alteration in DIM-7 expression results in proportional changes in the intensity of training-activated MAPK accumulated within the nuclei of mushroom body neurons during LTM consolidation. Such DIM-7-regulated nuclear accumulation of activated MAPK is observed only in the training specified for LTM induction and determines the amplitude, but not the time course, of memory consolidation.
authors.affiliation: Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
authors.forename: Qian
authors.initials: Q
authors.lastname: Li
authors.affiliation: Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
authors.forename: Xuchen
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
authors.forename: Wantong
authors.identifier: http://orcid.org/0000-0003-4836-9563
authors.initials: W
authors.lastname: Hu
authors.affiliation: School of Life Sciences, Peking University, Beijing 100871, China;
authors.forename: Xitong
authors.initials: X
authors.lastname: Liang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China;
authors.forename: Lianzhang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Shenzhen Key Laboratory for Orchid Conservation and Utilization, National Orchid Conservation Center of China and Orchid Conservation and Research Center of Shenzhen, Shenzhen 518114, China; Center for Biotechnology and Biomedicine, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China.
authors.forename: Zhong-Jian
authors.identifier: http://orcid.org/0000-0003-4390-3878
authors.initials: ZJ
authors.lastname: Liu
authors.affiliation: Tsinghua-Peking Center for Life Sciences, McGovern Institute for Brain Research, Ministry of Education Key Laboratory of Protein Sciences, School of Life Sciences, Tsinghua University, Beijing 100084, China; zhongyi@tsinghua.edu.cn.
authors.forename: Yi
authors.initials: Y
authors.lastname: Zhong
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology*; D002070:Butadienes / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism*; D003513:Cycloheximide / Q000494:pharmacology; D029721:Drosophila Proteins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004331:Drosophila melanogaster / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D006358:Hot Temperature; D028884:Karyopherins / Q000096:biosynthesis / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D020935:MAP Kinase Signaling System; D000069077:Memory Consolidation / Q000187:drug effects / Q000502:physiology*; D057567:Memory, Long-Term / Q000187:drug effects / Q000502:physiology*; D008570:Memory, Short-Term / Q000502:physiology; D015735:Mifepristone / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D024521:Mushroom Bodies / Q000166:cytology / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012903:Smell / Q000502:physiology; D013997:Time Factors
chemical_list: D002070:Butadienes; D029721:Drosophila Proteins; D028884:Karyopherins; C524335:Msk protein, Drosophila; D009570:Nitriles; D011993:Recombinant Fusion Proteins; C113580:U 0126; D015735:Mifepristone; D003513:Cycloheximide; D020928:Mitogen-Activated Protein Kinases
keywords: Drosophila; MAPK; consolidation; importin; long-term memory