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1000 Titel
  • A Jacob/Nsmf Gene Knockout Results in Hippocampal Dysplasia and Impaired BDNF Signaling in Dendritogenesis
1000 Autor/in
  1. Spilker, Christina |
  2. Nullmeier, Sven |
  3. Grochowska, Katarzyna |
  4. Schumacher, Anne |
  5. Butnaru, Ioana |
  6. Macharadze, Tamar |
  7. Monteiro Gomes, Guilherme |
  8. Yuanxiang, PingAn |
  9. BAYRAKTAR, Gonca |
  10. Rodenstein, Carolin |
  11. Geiseler, Carolin |
  12. Kolodziej, Angela |
  13. Lopez-Rojas, Jeffrey |
  14. Montag, Dirk |
  15. Angenstein, Frank |
  16. Bär, Julia |
  17. D’Hanis, Wolfgang |
  18. Roskoden, Thomas |
  19. Mikhaylova, Marina |
  20. Budinger, Eike |
  21. Ohl, Frank W. |
  22. Stork, Oliver |
  23. Zenclussen, Ana C. |
  24. Karpova, Anna |
  25. Schwegler, Herbert |
  26. Kreutz, Michael R. |
1000 Erscheinungsjahr 2016
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2016-03-15
1000 Erschienen in
1000 Quellenangabe
  • 12(3): e1005907
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2016
1000 Lizenz
1000 Verlagsversion
  • https://doi.org/10.1371/journal.pgen.1005907 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792503/ |
1000 Ergänzendes Material
  • http://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005907#sec033 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Jacob, the protein encoded by the Nsmf gene, is involved in synapto-nuclear signaling and docks an N-Methyl-D-Aspartate receptor (NMDAR)-derived signalosome to nuclear target sites like the transcription factor cAMP-response-element-binding protein (CREB). Several reports indicate that mutations in NSMF are related to Kallmann syndrome (KS), a neurodevelopmental disorder characterized by idiopathic hypogonadotropic hypogonadism (IHH) associated with anosmia or hyposmia. It has also been reported that a protein knockdown results in migration deficits of Gonadotropin-releasing hormone (GnRH) positive neurons from the olfactory bulb to the hypothalamus during early neuronal development. Here we show that mice that are constitutively deficient for the Nsmf gene do not present phenotypic characteristics related to KS. Instead, these mice exhibit hippocampal dysplasia with a reduced number of synapses and simplification of dendrites, reduced hippocampal long-term potentiation (LTP) at CA1 synapses and deficits in hippocampus-dependent learning. Brain-derived neurotrophic factor (BDNF) activation of CREB-activated gene expression plays a documented role in hippocampal CA1 synapse and dendrite formation. We found that BDNF induces the nuclear translocation of Jacob in an NMDAR-dependent manner in early development, which results in increased phosphorylation of CREB and enhanced CREB-dependent Bdnf gene transcription. Nsmf knockout (ko) mice show reduced hippocampal Bdnf mRNA and protein levels as well as reduced pCREB levels during dendritogenesis. Moreover, BDNF application can rescue the morphological deficits in hippocampal pyramidal neurons devoid of Jacob. Taken together, the data suggest that the absence of Jacob in early development interrupts a positive feedback loop between BDNF signaling, subsequent nuclear import of Jacob, activation of CREB and enhanced Bdnf gene transcription, ultimately leading to hippocampal dysplasia.
1000 Sacherschließung
lokal Developmental neuroscience
lokal Hippocampus
lokal Neurons
lokal Neuronal dendrites
lokal Animal behavior
lokal Mice
lokal Olfactory bulb
lokal Nuclear import
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
  1. http://orcid.org/0000-0002-7996-7673|https://frl.publisso.de/adhoc/creator/TnVsbG1laWVyLCBTdmVu|http://orcid.org/0000-0001-8298-176X|https://frl.publisso.de/adhoc/creator/U2NodW1hY2hlciwgQW5uZQ==|https://frl.publisso.de/adhoc/creator/QnV0bmFydSwgSW9hbmE=|https://frl.publisso.de/adhoc/creator/TWFjaGFyYWR6ZSwgVGFtYXI=|https://frl.publisso.de/adhoc/creator/TW9udGVpcm8gR29tZXMsIEd1aWxoZXJtZQ==|https://frl.publisso.de/adhoc/creator/WXVhbnhpYW5nLCBQaW5nQW4=|http://orcid.org/0000-0001-5476-4346|https://frl.publisso.de/adhoc/creator/Um9kZW5zdGVpbiwgQ2Fyb2xpbg==|https://frl.publisso.de/adhoc/creator/R2Vpc2VsZXIsIENhcm9saW4=|https://frl.publisso.de/adhoc/creator/S29sb2R6aWVqLCBBbmdlbGE=|http://orcid.org/0000-0001-9648-4051|http://orcid.org/0000-0002-4964-1330|https://frl.publisso.de/adhoc/creator/QW5nZW5zdGVpbiwgRnJhbms=|https://frl.publisso.de/adhoc/creator/QsOkciwgSnVsaWE=|https://frl.publisso.de/adhoc/creator/ROKAmUhhbmlzLCBXb2xmZ2FuZw==|https://frl.publisso.de/adhoc/creator/Um9za29kZW4sIFRob21hcw==|https://frl.publisso.de/adhoc/creator/TWlraGF5bG92YSwgTWFyaW5h|http://orcid.org/0000-0003-2420-8159|https://frl.publisso.de/adhoc/creator/T2hsLCBGcmFuayBXLg==|https://frl.publisso.de/adhoc/creator/U3RvcmssIE9saXZlcg==|https://frl.publisso.de/adhoc/creator/WmVuY2x1c3NlbiwgQW5hIEMu|https://frl.publisso.de/adhoc/creator/S2FycG92YSwgQW5uYQ==|https://frl.publisso.de/adhoc/creator/U2Nod2VnbGVyLCBIZXJiZXJ0|https://frl.publisso.de/adhoc/creator/S3JldXR6LCBNaWNoYWVsIFIu
1000 Label
1000 Förderer
  1. Alexander-von-Humboldt Foundation |
  2. NPlast |
  3. Deutsche Forschungsgemeinschaft (DFG) |
  4. Bundesministerium für Forschung und Technologie (BMBF/Energi) |
  5. EU Joint Programme – Neurodegenerative Disease Research (JPND) |
  6. Leibniz Foundation |
  7. Marie Curie Actions |
  8. European Union |
1000 Fördernummer
  1. -
  2. EU-PP7 MC-ITN
  3. GRK 1167; SFB779 TP B08; Kr1879 /5-1; Kr1879 / 6-1; Ml 1923/1-1; Sto488/4-1; SFB779 TP B05; SFB TP B01
  4. -
  5. -
  6. -
  7. -
  8. FP7/2007-2013/; 289581
1000 Förderprogramm
  1. -
  2. -
  3. Emmy-Noether Programm
  4. -
  5. STAD
  6. Pakt für Forschung
  7. People Prgogramme
  8. Seventh Framework Programme
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer Alexander-von-Humboldt Foundation |
    1000 Förderprogramm -
    1000 Fördernummer -
  2. 1000 joinedFunding-child
    1000 Förderer NPlast |
    1000 Förderprogramm -
    1000 Fördernummer EU-PP7 MC-ITN
  3. 1000 joinedFunding-child
    1000 Förderer Deutsche Forschungsgemeinschaft (DFG) |
    1000 Förderprogramm Emmy-Noether Programm
    1000 Fördernummer GRK 1167; SFB779 TP B08; Kr1879 /5-1; Kr1879 / 6-1; Ml 1923/1-1; Sto488/4-1; SFB779 TP B05; SFB TP B01
  4. 1000 joinedFunding-child
    1000 Förderer Bundesministerium für Forschung und Technologie (BMBF/Energi) |
    1000 Förderprogramm -
    1000 Fördernummer -
  5. 1000 joinedFunding-child
    1000 Förderer EU Joint Programme – Neurodegenerative Disease Research (JPND) |
    1000 Förderprogramm STAD
    1000 Fördernummer -
  6. 1000 joinedFunding-child
    1000 Förderer Leibniz Foundation |
    1000 Förderprogramm Pakt für Forschung
    1000 Fördernummer -
  7. 1000 joinedFunding-child
    1000 Förderer Marie Curie Actions |
    1000 Förderprogramm People Prgogramme
    1000 Fördernummer -
  8. 1000 joinedFunding-child
    1000 Förderer European Union |
    1000 Förderprogramm Seventh Framework Programme
    1000 Fördernummer FP7/2007-2013/; 289581
1000 Objektart article
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1000 @id frl:6404295.rdf
1000 Erstellt am 2017-09-04T15:29:32.174+0200
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1000 Zuletzt bearbeitet Mon Dec 07 16:57:03 CET 2020
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