title: Novel insights in FGFR1 regulation: lessons from Kallmann syndrome.
abstract: Disrupted fibroblast growth factor receptor (FGFR)1 signalling has been shown to cause Kallmann syndrome (KS), a human genetic disorder characterised by olfactory bulb dysgenesis and hypogonadotrophic hypogonadism. Loss-of-function mutations in the KS gene KAL-2/FGFR1 account for roughly 10% of KS cases, leading to the autosomal dominant form of the disease. Anosmin-1, the KAL-1 gene product underlying X-linked KS, modulates FGFR1 signalling via regulation of FGF2/FGFR1/heparin signalling complex assembly and activity. This review covers recent advances in the potential interactions of KS-associated molecules within the FGFR1 signalling complex, and demonstrates a novel mechanism of pre-signalling modulation that mechanistically links an autosomal dominant and sex-linked mode of inheritance of this disease, highlighting the central role of FGFR1 signalling in KS.
authors.affiliation: Centre for Neuroendocrinology, UCL Medical School, Royal Free Campus, London NW3 2QG, UK. y.hu@medsch.ucl.ac.uk
authors.forename: Youli
authors.initials: Y
authors.lastname: Hu
authors.forename: Pierre-Marc
authors.initials: PM
authors.lastname: Bouloux
mesh_terms: D006801:Humans; D040582:Inheritance Patterns / Q000235:genetics; D017436:Kallmann Syndrome / Q000235:genetics / Q000503:physiopathology*; D051496:Receptor, Fibroblast Growth Factor, Type 1 / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D051496:Receptor, Fibroblast Growth Factor, Type 1