NGF-induced moesin phosphorylation is mediated by the PI3K, Rac1 and Akt and required for neurite formation in PC12 cells

• Published in: Neurochemistry international 2010-05, Vol.56 (6), p.810-818
• Main Authors: Jeon, Songhee, Park, Jung-Keug, Bae, Chang-Dae, Park, Joobae
• Format: Article
• Language: English
• Subjects: Akt; Animals; Biological and medical sciences; Cell Differentiation; Enzyme Activation; Fundamental and applied biological sciences. Psychology; Microfilament Proteins - genetics; Microfilament Proteins - metabolism; Moesin; Mutation; Nerve Growth Factor - pharmacology; Neurite outgrowth; Neurites - drug effects; Neurites - physiology; NGF; PC12 Cells; Phosphatidylinositol 3-Kinases - metabolism; Phosphorylation - drug effects; PI3K; Proto-Oncogene Proteins c-akt - metabolism; Rac1; rac1 GTP-Binding Protein - metabolism; Rats; Signal Transduction - drug effects; Substrate Specificity; Threonine - metabolism; Transfection; Vertebrates: nervous system and sense organs
• ISSN: 0197-0186; 1872-9754
• DOI: 10.1016/j.neuint.2010.03.005

Moesin is a member of ERM family proteins which act as the cross-linkers between plasma membrane and actin-cytoskeleton and is activated by phosphorylation at Thr-558. In neurons, suppression of radixin and moesin alters the growth cone morphology. However, the significance of phosphorylation of ERM proteins in neuronal cells has not been fully investigated. In this study, we studied the signaling pathways responsible for moesin phosphorylation and its functional importance in NGF-treated PC12 cells. NGF rapidly induced the phosphorylation of moesin at Thr-558 in PC12 cells which was dependent on PI3K and Rac1. We found that Akt interacted and phosphorylated with moesin both in vitro and in vivo. Inhibition of PI3K and Rac1 abolished the NGF-induced Akt activation, indicating that Akt is at the downstream of PI3K and Rac1. To examine the functional role of phosphorylated ERM proteins, a dominant negative mutant form of moesin (T558A) was introduced into PC12 cells. The mutant significantly reduced the frequency of cells with neurites following NGF treatment. Our results indicate that PI3K, Rac1 and Akt-dependent phosphorylation of moesin is required for the NGF-induced neurite formation in differentiating PC12 cells.