[Abstract Title]. - Society for Neuroscience

Title: NCAM signaling through the FGF receptor in health and disease
Authors: *V. BEREZIN 1 , S. LI 2 , D. K. DITLEVSEN 2 , E. BOCK 1 ;
1 Neurosci& Pharmacol, Protein Lab., Copenhagen 2200, Denmark; 2 ENKAM Pharmaceuticals
A/S, Copenhagen, Denmark
Abstract: Stimulation of the neural cell adhesion molecule (NCAM) by homophilic interactions
induces activation of a number of signaling molecules, including the fibroblast growth factor
(FGF) receptor, non-receptor tyrosine kinases Fyn and FAK, growth associated protein GAP-43,
the MAP kinase pathway, protein kinases A, C and G, and intracellular calcium. The role of
NCAM signaling through FGF receptor has been addressed employing a variety of experimental
approaches. A direct interaction between the fibronectin type III (FN3) modules of NCAM has
recently been demonstrated by nuclear magnetic resonance (NMR) and surface plasmon
resonance (SPR) analyses. Using structural data, bioinformatics and SPR binding analysis six
sequence motifs, four in the first and two in the second FN3 modules of NCAM, involved in
interactions with the FGF receptor have been identified. Synthetic peptides corresponding to
these motifs constitute valuable pharmacological tools for the study of NCAM and FGF receptor
signaling properties. All six peptides are agonists of the FGF receptor. In vitro, they all induce
receptor phosphorylation and promote neurite outgrowth of primary neurons. One of the
peptides, termed FGL, and a cognate ligand, FGF1, are shown to have different kinetics of
receptor activation and activation of downstream signaling molecules such as phospholipase C
(PLC)-gamma, FGF receptor substrate (FRS)-2 and Src homology and collagen (Shc). This
suggests that NCAM signaling through the FGF receptor differs from signaling events induced
by FGFs. In vivo, the FGL peptide enhances synaptic plasticity and improves cognition under
normal and pathological conditions.
Disclosures: V. Berezin , ENKAM Pharmaceuticals, E. Ownership Interest (stock, stock
options, patent or other intellectual property); S. Li, None; D.K. Ditlevsen, None; E. Bock,
ENKAM Pharmaceuticals, E. Ownership Interest (stock, stock options, patent or other
intellectual property).
Poster
290. Animal Cognition and Behavior: Learning and Memory: Pharmacology I
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm
Program#/Poster#: 290.5/RR56
Topic: F.02.j. Learning and memory: Pharmacology
Support: NIA Grant AG009525