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 determine 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.
Department of Basic and Applied Medical Sciences, University G. d'Annunzio, Chieti-Pescara, Italy. mariggio@unich.it
Maria A
MA
Mariggiò
Caterina
C
Morabito
Simone
S
Guarnieri
Antonietta
A
Gentile
Kateryna
K
Kolkova
Giorgio
G
Fanò
D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects; D004789:Enzyme Activation; D005707:Gallic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D019950:Mitogen-Activated Protein Kinase 1 / Q000502:physiology; D048052:Mitogen-Activated Protein Kinase 3 / Q000502:physiology; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis*; D009842:Oligopeptides / Q000494:pharmacology*; D016716:PC12 Cells; D017434:Protein Structure, Tertiary; D021381:Protein Transport; D051381:Rats; D014162:Transfection
D019006:Neural Cell Adhesion Molecules; D009842:Oligopeptides; C532437:aspartyl-aspartyl-seryl-aspartyl-glutamyl-glutamyl-asparagine; C006014:8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate; D005707:Gallic Acid; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3