Phospholipase D2 functions as a downstream signaling molecule of MAP kinase pathway in L1‐stimulated neurite outgrowth of cerebellar granule neurons

• DOI: 10.1111/j.1471-4159.2004.02308.x
• Publication Date: 2006-05-11T12:17:12Z
• Authors: Hiroshi Watanabe; Masakazu Yamazaki; Hideyuki Miyazaki; Chihiro Arikawa; Kouichi Itoh; Takehiko Sasaki; Tomohiko Maehama; Michael A. Frohman; Yasunori Kanaho
• Keywords: Neurite; PLD2; Phospholipase D; Growth cone

Stimulation of the neuronal cell adhesion molecule L1 in cerebellar granule neurons (CGNs) enhances neurite outgrowth and this response is inhibited by primary alcohol ethanol. Because alcohols suppress formation signaling lipid phosphatidic acid (PA) phospholipase D (PLD), observation prompted us to investigate whether PLD plays a role L1-mediated CGNs. In cerebellum postnatal day 8 mice, PLD2 protein was abundantly expressed, while PLD1 expression not detected. The L1-stimulated overexpression lipase-deficient PLD2. Increases cellular PA levels direct application or wild-type mimicked L1-dependent stimulation outgrowth. Furthermore, it found that CGNs increased activity concomitantly with phosphorylation extracellular signal-regulated kinase (ERK), both which were MAP kinase-ERK (MEK) inhibitor. These results provide evidence functions as downstream ERK mediate CGNs, mechanism may be related alcohol-related neurodevelopmental disorders.