The motor protein kinesin-1 links neurofibromin and merlin in a common cellular pathway of neurofibromatosis.
Mutations in either of the two tumor suppressor genes NF1 (neurofibromin) and NF2 (merlin) result in Neurofibromatosis, a condition predisposing individuals to developing a variety of benign and malignant tumors of the central and peripheral nervous systems. Here we report the identification of two distinct NF1-containing complexes, one in the soluble and the other in the particulate fraction of HeLa extract. We show that the soluble NF1 complex delineates a large holo-NF1 complex (2 MDa) encompassing the components of a smaller particulate core-NF1 complex (400 kDa). Purification of the core-NF1 complex followed by mass spectrometric analysis revealed the motor protein, kinesin-1 heavy chain (HsuKHC/KIF5B), as a catalytic subunit of both NF-1-containing complexes. Importantly, although NF1 and NF2 are not in a stable association, NF2 is also a component of a distinct kinesin-1-containing complex. These results point to kinesin-1 as a common denominator between NF1 and NF2.
Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Mohamed-Ali
MA
Hakimi
David W
DW
Speicher
Ramin
R
Shiekhattar
D000818:Animals; D001921:Brain / Q000378:metabolism; D002417:Cattle; D002853:Chromatography, Liquid / Q000379:methods; D006367:HeLa Cells; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D009456:Neurofibromatosis 1 / Q000235:genetics*; D025542:Neurofibromin 1 / Q000235:genetics / Q000378:metabolism*; D025581:Neurofibromin 2 / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D025542:Neurofibromin 1; D025581:Neurofibromin 2; D011994:Recombinant Proteins; D016547:Kinesins