TY - JOUR
T1 - Identification of neural cell adhesion molecule L1-derived neuritogenic ligands of the fibroblast growth factor receptor
AU - Kulahin, Nikolaj
AU - Li, Shizhong
AU - Kiselyov, Vladislav
AU - Bock, Elisabeth
AU - Berezin, Vladimir
N1 - Keywords: Amino Acid Motifs; Amino Acid Sequence; Animals; Cell Differentiation; Cell Line; Cells, Cultured; Central Nervous System; Dose-Response Relationship, Drug; Humans; Ligands; Neural Cell Adhesion Molecule L1; Neurites; Neurogenesis; Peptides; Phosphorylation; Protein Binding; Rats; Receptors, Fibroblast Growth Factor; Up-Regulation
PY - 2009
Y1 - 2009
N2 - 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.
AB - 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.
U2 - 10.1002/jnr.22014
DO - 10.1002/jnr.22014
M3 - Journal article
C2 - 19185025
SN - 0360-4012
VL - 87
SP - 1806
EP - 1812
JO - Journal of Neuroscience Research
JF - Journal of Neuroscience Research
IS - 8
ER -