title: ERK1/2 signaling is essential for the chemoattraction exerted by human FGF2 and human anosmin-1 on newborn rat and mouse OPCs via FGFR1.
abstract: 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 (FGFR1) 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 FGFR1 on neuronal precursors from the subventricular zone (SVZ) and the essential role of the ERK1/2 signaling. We report here the positive chemotactic effect of FGF2 and anosmin-1 on rat and mouse postnatal OPCs via FGFR1. The same effect was observed with the truncated N-terminal region of anosmin-1 (A1Nt). The introduction in anosmin-1 of the missense mutation F517L found in patients suffering from KS annulled the chemotactic activity; however, the mutant form carrying the disease-causing mutation E514K also found in KS patients, behaved as the wild-type protein. The chemoattraction exhibited by FGF2 and anosmin-1 on OPCs was blocked by the mitogen-activated protein kinase (MAPK) inhibitor U0126, suggesting that the activation of the ERK1/2 MAPK signaling pathway following interaction with the FGFR1 is necessary for FGF2 and anosmin-1 to exert their chemotactic effect. In fact, both proteins were able to induce the phosphorylation of the ERK1/2 kinases after the activation of the FGFR1 receptor.
authors.affiliation: Grupo de Neurobiología del Desarrollo-GNDe, Hospital Nacional de Parapléjicos, Finca "La Peraleda, s/n, E-45071-Toledo, Spain.
authors.forename: Verónica
authors.initials: V
authors.lastname: Murcia-Belmonte
authors.forename: Eva M
authors.initials: EM
authors.lastname: Medina-Rodríguez
authors.forename: Ana
authors.initials: A
authors.lastname: Bribián
authors.forename: Fernando
authors.initials: F
authors.lastname: de Castro
authors.forename: Pedro F
authors.initials: PF
authors.lastname: Esteban
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D002478:Cells, Cultured; D002633:Chemotaxis / Q000187:drug effects / Q000502:physiology*; D003412:Cricetulus; D004791:Enzyme Inhibitors / Q000494:pharmacology; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000235:genetics / Q000378:metabolism*; D005732:Gangliosides / Q000378:metabolism; D006801:Humans; D020547:Lateral Ventricles / Q000166:cytology; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation / Q000235:genetics; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D000076104:Oligodendrocyte Transcription Factor 2; D009836:Oligodendroglia / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology*; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D004791:Enzyme Inhibitors; D016326:Extracellular Matrix Proteins; D016222:Fibroblast Growth Factor 2; D005732:Gangliosides; D009419:Nerve Tissue Proteins; D000076104:Oligodendrocyte Transcription Factor 2; D051496:Receptor, Fibroblast Growth Factor, Type 1; C076266:ANOS1 protein, human; C512773:Olig2 protein, mouse; C062875:ganglioside A2B5; C496348:FGFR1 protein, human
keywords: Kallmann syndrome; migration; oligodendrocyte precursor; remyelination