Neurofibromatosis type 1 protein and amyloid precursor protein interact in normal human melanocytes and colocalize with melanosomes.
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.
De Schepper
Sofie
S
Department of Dermatology, Ghent University Hospital, Ghent, Belgium. sofie.deschepper@ugent.be
Boucneau
Joachim M A
JM
Westbroek
Wendy
W
Mommaas
Mieke
M
Onderwater
Jos
J
Messiaen
Ludwine
L
Naeyaert
Jean-Marie A D
JM
Lambert
Jo L W
JL
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
D025542:Neurofibromin 1; D000685:Serum Amyloid A Protein