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Identification of neural cell adhesion molecule L1‐derived neuritogenic ligands of the fibroblast growth factor receptor
Author(s) -
Kulahin Nikolaj,
Li Shizhong,
Kiselyov Vladislav,
Bock Elisabeth,
Berezin Vladimir
Publication year - 2009
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.22014
Subject(s) - fibroblast growth factor receptor , neurite , fgf1 , fibroblast growth factor , receptor , neural cell adhesion molecule , microbiology and biotechnology , fibronectin , biology , phosphorylation , cell adhesion molecule , cell adhesion , chemistry , biochemistry , cell , in vitro
Abstract The neural cell adhesion molecule L1 plays an important role in axon growth, neuronal survival, and synaptic plasticity. We recently demonstrated that the L1 fibronectin type III (FN3) modules interact directly with the fibroblast growth factor (FGF) receptor (FGFR). Sequence alignment of individual L1 FN3 modules with various FGFs suggested that four sequence motifs located in the third and fifth L1 FN3 modules might be involved in interactions with FGFR. The present study found that corresponding synthetic peptides, termed elcamins 1 , 2 , 3 , and 4 , bind and activate FGFR in the absence of FGF1. Conversely, in the presence of FGF1, elcamins inhibited receptor phosphorylation, indicating that the peptides are FGFR partial agonists. Elcamins 1, 3, and 4 dose dependently induced neurite outgrowth in cultured primary cerebellar neurons. The neuritogenic effect of elcamins was dependent on FGFR activation, insofar as the effect was abolished by the receptor inhibition. Thus, the identified peptides act as L1 mimetics with regard to activation of FGFR and induction of neurite outgrowth. © 2009 Wiley‐Liss, Inc.