A peptide against the N-terminus of myristoylated alanine-rich C kinase substrate promotes neuronal differentiation in SH-SY5Y human neuroblastoma cells.

Myristoylated alanine-rich protein kinase C substrate (MARCKS) plays crucial roles in neuronal functions and differentiation. However, specific effects of the myristoylated N-terminal sequence (MANS) peptide, a widely used MARCKS modulator comprising the initial 24 amino acids of MARCKS, on neuronal cells remain unclear. Therefore, in this study, we aimed to examine the effects and action mechanisms of the MANS peptide on SH-SY5Y human neuroblastoma cells, which served as the in vitro neuronal cell models. MANS treatment of SH-SY5Y cells resulted in significant neurite outgrowth within 24 hr, which was as prominent as that induced by seven days of treatment with all-trans retinoic acid, the most common agent used to induce SH-SY5Y cell differentiation. Levels of synaptophysin, a neuronal marker protein, were significantly increased in the MANS peptide-treated cells. Additionally, increased MARCKS levels and decreased MARCKS phosphorylation were observed in MANS peptide-treated cells. Notably, neurite outgrowth induced by the MANS peptide was significantly reduced in MARCKS-knocked-down cells. Overall, these results suggest the MANS peptide as a novel agent for SH-SY5Y cell differentiation, particularly for the analysis of MARCKS functions.