PLD1 participates in BDNF-induced signalling in cortical neurons

被引:25
作者
Ammar, Mohamed Raafet [1 ,2 ]
Thahouly, Tamou [1 ,2 ]
Hanauer, Andre [3 ,4 ]
Stegner, David [5 ,6 ]
Nieswandt, Bernhard [5 ,6 ]
Vitale, Nicolas [1 ,2 ]
机构
[1] CNRS, INCI, UPR 3212, F-67084 Strasbourg, France
[2] Univ Strasbourg, F-67084 Strasbourg, France
[3] CNRS, INSERM, IGBMC, F-67404 Illkirch Graffenstaden, France
[4] Univ Strasbourg, F-67404 Illkirch Graffenstaden, France
[5] Univ Wurzburg, Dept Expt Biomed, Univ Hosp, D-97080 Wurzburg, Germany
[6] Rudolf Virchow Ctr, D-97080 Wurzburg, Germany
关键词
COFFIN-LOWRY-SYNDROME; LONG-TERM POTENTIATION; ERK MAP KINASE; NEUROTROPHIC FACTOR; PHOSPHATIDIC-ACID; PHOSPHOLIPASE D1; NEURITE OUTGROWTH; DENDRITIC GROWTH; PROTEIN RSK2; PHOSPHORYLATION;
D O I
10.1038/srep14778
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页数:11
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