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PLD1 participates in BDNF-induced signalling in cortical neurons

Please always quote using this URN: urn:nbn:de:bvb:20-opus-139962
  • The brain-derived neurotrophic factor BDNF plays a critical role in neuronal development and the induction of L-LTP at glutamatergic synapses in several brain regions. However, the cellular and molecular mechanisms underlying these BDNF effects have not been firmly established. Using in vitro cultures of cortical neurons from knockout mice for Pld1 and Rsk2, BDNF was observed to induce a rapid RSK2-dependent activation of PLD and to stimulate BDNF ERK1/2-CREB and mTor-S6K signalling pathways, but these effects were greatly reduced inThe brain-derived neurotrophic factor BDNF plays a critical role in neuronal development and the induction of L-LTP at glutamatergic synapses in several brain regions. However, the cellular and molecular mechanisms underlying these BDNF effects have not been firmly established. Using in vitro cultures of cortical neurons from knockout mice for Pld1 and Rsk2, BDNF was observed to induce a rapid RSK2-dependent activation of PLD and to stimulate BDNF ERK1/2-CREB and mTor-S6K signalling pathways, but these effects were greatly reduced in Pld1\(^{-/-}\) neurons. Furthermore, phospho-CREB did not accumulate in the nucleus, whereas overexpression of PLD1 amplified the BDNF-dependent nuclear recruitment of phospho-ERK1/2 and phospho-CREB. This BDNF retrograde signalling was prevented in cells silenced for the scaffolding protein PEA15, a protein which complexes with PLD1, ERK1/2, and RSK2 after BDNF treatment. Finally PLD1, ERK1/2, and RSK2 partially colocalized on endosomal structures, suggesting that these proteins are part of the molecular module responsible for BDNF signalling in cortical neurons.show moreshow less

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Metadaten
Author: Mohamed Raafet Ammar, Tamou Thahouly, André Hanauer, David Stegner, Bernhard Nieswandt, Nicolas Vitale
URN:urn:nbn:de:bvb:20-opus-139962
Document Type:Journal article
Faculties:Fakultät für Biologie / Rudolf-Virchow-Zentrum
Medizinische Fakultät / Institut für Experimentelle Biomedizin
Language:English
Parent Title (English):Scientific Reports
Year of Completion:2015
Volume:5
Issue:14778
Source:Scientific Reports 5, 14778; doi: 10.1038/srep14778 (2015)
DOI:https://doi.org/10.1038/srep14778
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
Tag:ERK map kinease; brain; coffin-lowry-syndrome; dendritic growth; long-term potentation; neurite outgrowth; neurotrophic factor; phosphatidic acid; phospholipase D; protein RSK2
Release Date:2016/11/04
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung