title: PLD1 participates in BDNF-induced signalling in cortical neurons.
abstract: 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 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.
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR-3212 Centre National de la Recherche Scientifique &Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France.
authors.forename: Mohamed Raafet
authors.initials: MR
authors.lastname: Ammar
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR-3212 Centre National de la Recherche Scientifique &Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France.
authors.forename: Tamou
authors.initials: T
authors.lastname: Thahouly
authors.affiliation: Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Centre National de la Recherche Scientifique, Institut National de la Santé et de la Recherche Médicale &Université de Strasbourg, BP 10142, 67404 Illkirch Cedex, France.
authors.forename: André
authors.initials: A
authors.lastname: Hanauer
authors.affiliation: University of Würzburg, Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center; Josef-Schneider-Straße 2; D15, 97080 Würzburg, Germany.
authors.forename: David
authors.initials: D
authors.lastname: Stegner
authors.affiliation: University of Würzburg, Department of Experimental Biomedicine, University Hospital and Rudolf Virchow Center; Josef-Schneider-Straße 2; D15, 97080 Würzburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Nieswandt
authors.affiliation: Institut des Neurosciences Cellulaires et Intégratives (INCI), UPR-3212 Centre National de la Recherche Scientifique &Université de Strasbourg, 5 rue Blaise Pascal, 67084 Strasbourg, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Vitale
mesh_terms: D000818:Animals; D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D017362:Cyclic AMP Response Element-Binding Protein / Q000235:genetics / Q000378:metabolism; D011992:Endosomes / Q000378:metabolism; D005786:Gene Expression Regulation; D051379:Mice; D018345:Mice, Knockout; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010739:Phospholipase D / Q000172:deficiency / Q000235:genetics*; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D061251:Primary Cell Culture; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism
chemical_list: D051017:Apoptosis Regulatory Proteins; D019208:Brain-Derived Neurotrophic Factor; D017362:Cyclic AMP Response Element-Binding Protein; C490444:Pea15 protein, mouse; D010750:Phosphoproteins; D034741:RNA, Small Interfering; C546843:mTOR protein, mouse; D038744:Ribosomal Protein S6 Kinases, 90-kDa; C512964:Rps6ka1 protein, mouse; D058570:TOR Serine-Threonine Kinases; C069330:ribosomal protein S6 kinase, 90kDa, polypeptide 3; C535148:Mapk1 protein, mouse; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D010739:Phospholipase D; C106801:phospholipase D1