IgIII (270-280)-fragment-like H2N-DDSDEEN-COOH peptide modulates N-CAM expression via Ca2+-dependent ERK signaling during {"}in vitro neurogenesis{"}

the two major isoforms (180 kDa and 140 kDa) of the neural cell adhesion molecule (N-CAM) are crucially involved in neurogenesis and brain repair via activation of the mitogen-activated protein kinase (MAPK) cascade. modification by glycosylation, and homophilic and heterophilic interactions regulate the function of N-CAM, but little is known about the interplay of these processes. In the neuron-like PC12 cell line, extracellular small acidic peptides have been shown to modulate the expression of N-CAM mRNA and protein and regulate its translocation to the plasma membrane. among these peptides, a synthetic Ig-III-like short sequence (H2N-DDSDEEN-COOH), designated sSP, was particularly potent. in this study, we analyzed the cross-talk between nerve growth factor (NGF) and extracellular sSP in native and N-CAM-transfected PC12 cells to deter-mine if these systems interact to modulate transduction pathways and regulate early steps of neurogenesis in vitro. our results indicate that sSP accelerated the phosphorylation of extracellular regulated kinase-1 (ERK1) and -2 (ERK2) and promoted plasma membrane translocation of 180 kDa N-CAM. By stabilizing cell-cell contacts and promoting cell cluster formation, these events, which were mediated via a significant increase in intracellular Ca2+, regulated some of the early stages of the NGF-induced differentiation process.