title: Neurofibromatosis type 1 protein and amyloid precursor protein interact in normal human melanocytes and colocalize with melanosomes.
abstract: The neurofibromatosis type 1 (NF1) gene product, neurofibromin, is known to interact with Ras, thereby negatively regulating its growth-promoting function. Although this is a well-established interaction, the discovery of other neurofibromin interacting partners could reveal new functional properties of this large protein. Using yeast two-hybrid analysis against a brain cDNA library, we identified a novel interaction between the amyloid precursor protein and the GTPase activating protein-related domain of neurofibromin. This interaction was further analyzed in human melanocytes and confirmed by immunoprecipitation and colocalization studies. In addition, we observed a colocalization of amyloid precursor protein and neurofibromin with melanosomes. Amyloid precursor protein has been proposed to function as a vesicle cargo receptor for the motor protein kinesin-1 in neurons. This colocalization of amyloid precursor protein and neurofibromin with melanosomes was lost in melanocytes obtained from normal skin of a NF1 patient. We suggest that a complex between amyloid precursor protein, neurofibromin, and melanosomes might be important in melanosome transport, which could shed a new light on the etiopathogenesis of pigment-cell-related manifestations in NF1.
authors.affiliation: Department of Dermatology, Ghent University Hospital, Ghent, Belgium. sofie.deschepper@ugent.be
authors.forename: Sofie
authors.initials: S
authors.lastname: De Schepper
authors.forename: Joachim M A
authors.initials: JM
authors.lastname: Boucneau
authors.forename: Wendy
authors.initials: W
authors.lastname: Westbroek
authors.forename: Mieke
authors.initials: M
authors.lastname: Mommaas
authors.forename: Jos
authors.initials: J
authors.lastname: Onderwater
authors.forename: Ludwine
authors.initials: L
authors.lastname: Messiaen
authors.forename: Jean-Marie A D
authors.initials: JM
authors.lastname: Naeyaert
authors.forename: Jo L W
authors.initials: JL
authors.lastname: Lambert
mesh_terms: D019080:Cafe-au-Lait Spots / Q000209:etiology; D002478:Cells, Cultured; D016514:Genes, Neurofibromatosis 1; D006801:Humans; D008544:Melanocytes / Q000737:chemistry*; D020460:Melanosomes / Q000737:chemistry*; D025542:Neurofibromin 1 / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D000685:Serum Amyloid A Protein / Q000032:analysis* / Q000235:genetics / Q000378:metabolism; D020798:Two-Hybrid System Techniques
chemical_list: D025542:Neurofibromin 1; D000685:Serum Amyloid A Protein