PLD1 participates in BDNF-induced signalling in cortical neurons

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Signaling

Background:

• Brain-derived neurotrophic factor (BDNF) is vital for neuronal development and synaptic plasticity.
• The precise cellular and molecular mechanisms of BDNF signaling remain incompletely understood.

Purpose of the Study:

• To elucidate the role of phospholipase D1 (PLD1) and RSK2 in BDNF-induced signaling pathways.
• To investigate the molecular complex and localization involved in BDNF retrograde signaling.

Main Methods:

• Utilized in vitro cultures of cortical neurons from knockout mice for Pld1 and Rsk2.
• Employed techniques to assess signaling pathway activation (ERK1/2, CREB, S6K) and protein localization.
• Investigated the effect of PLD1 overexpression and PEA15 silencing.

Main Results:

• BDNF rapidly activated RSK2-dependent PLD, which was significantly reduced in Pld1(-/-) neurons.
• BDNF-stimulated ERK1/2-CREB and mTor-S6K pathways were impaired in Pld1(-/-) neurons.
• PLD1 overexpression enhanced BDNF-dependent nuclear recruitment of phospho-ERK1/2 and phospho-CREB; PEA15 silencing blocked retrograde signaling.

Conclusions:

• PLD1 and RSK2 are essential components of BDNF-induced signaling pathways in cortical neurons.
• PLD1, ERK1/2, and RSK2 form a molecular module, potentially localized on endosomes, mediating BDNF retrograde signaling via PEA15.