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

Maria A. Mariggiò, Caterina Morabito, Simone Guarnieri, Antonietta Gentile, Kateryna Kolkova, Giorgio Fanò

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)1486-1497
Number of pages12
Issue number9
Publication statusPublished - Sep 2008


  • Ig-III sequences
  • N-CAM
  • Neurogenesis
  • NGF
  • PC12 cells

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology
  • Physiology
  • Cellular and Molecular Neuroscience


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