FGFR1 and anosmin-1 underlying genetically distinct forms of Kallmann syndrome are co-expressed and interact in olfactory bulbs.
Kallmann syndrome is a genetically heterogeneous developmental disease characterised by a partial or complete lack of olfactory bulb development. Two genes underlying this disease have so far been identified: the KAL-1 gene, which encodes anosmin-1, an extracellular matrix protein that promotes axonal guidance and branch formation in vitro; and KAL-2, which encodes the known FGFR1. The implication of FGFR1 and anosmin-1 in the same developmental disease led us to test whether anosmin-1 and FGFR1 interact during the development of the olfactory system. In this paper, we showed that the two proteins co-localise in the olfactory bulb during development in rat. Using cross-immunoprecipitation assays of olfactory bulb extracts, we also demonstrated that anosmin-1 and FGFR1 are comprised within the same protein complex. Moreover, we show that anosmin-1 expression in CHO transfected cells increases FGFR1 accumulation, suggesting that anosmin-1 may act as a positive extracellular regulator of FGFR1 signalling. Taken together, our findings strongly suggest that anosmin-1 is an essential component of a FGFR1 pathway that plays a key role during olfactory bulb morphogenesis.
Ayari
Besma
B
INSERM U-616, Equipe Avenir, CHU Pitié-Salpêtrière 47 Bd de l'Hôpital, 75651, Paris Cedex 13, France.
Soussi-Yanicostas
Nadia
N
D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D003412:Cricetulus; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D017436:Kallmann Syndrome / Q000196:embryology / Q000235:genetics* / Q000378:metabolism; D008954:Models, Biological; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000378:metabolism; D009830:Olfactory Bulb / Q000002:abnormalities* / Q000196:embryology / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D017208:Rats, Wistar; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
C076266:ANOS1 protein, human; D016326:Extracellular Matrix Proteins; D009419:Nerve Tissue Proteins; C496348:FGFR1 protein, human; C496350:Fgfr1 protein, rat; D051496:Receptor, Fibroblast Growth Factor, Type 1