ERK1/2 signaling is essential for the chemoattraction exerted by human FGF2 and human anosmin-1 on newborn rat and mouse OPCs via FGFR1.

[kallmann syndrome]

Signaling through fibroblast growth factor receptors (FGFRs ) is essential for many cellular processes including proliferation and migration , as well as differentiation events such as myelination . Anosmin-1 is an extracellular matrix (ECM ) glycoprotein that interacts with the fibroblast growth factor receptor 1 (FGFR 1 ) to exert its biological actions through this receptor , although the intracellular pathways underlying anosmin-1 signaling remain largely unknown . This protein is defective in the X-linked form of Kallmann syndrome (KS ) and has a prominent role in the migration of neuronal and oligodendroglial precursors . We have shown that anosmin-1 exerts a chemotactic effect via FGFR 1 on neuronal precursors from the subventricular zone (SVZ ) and the essential role of the ERK 1 /2 signaling . We report here the positive chemotactic effect of FGF 2 and anosmin-1 on rat and mouse postnatal OPCs via FGFR 1 . The same effect was observed with the truncated N-terminal region of anosmin-1 (A 1 Nt ). The introduction in anosmin-1 of the missense mutation F 5 17 L found in patients suffering from KS annulled the chemotactic activity ; however , the mutant form carrying the disease-causing mutation E 514 K also found in KS patients , behaved as the wild-type protein . The chemoattraction exhibited by FGF 2 and anosmin-1 on OPCs was blocked by the mitogen-activated protein kinase (MAPK ) inhibitor U 0126 , suggesting that the activation of the ERK 1 /2 MAPK signaling pathway following interaction with the FGFR 1 is necessary for FGF 2 and anosmin-1 to exert their chemotactic effect . In fact , both proteins were able to induce the phosphorylation of the ERK 1 /2 kinases after the activation of the FGFR 1 receptor .