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Papers In Press, published online ahead of print August 20, 2002
J. Biol. Chem, 10.1074/jbc.C200434200
Submitted on July 31, 2002
Revised on August 14, 2002
Accepted on August 20, 2002

The motor protein kinesin-1 links neurofibromin and merlin in a common cellular pathway of neurofibromatosis

Mohamed-Ali Hakimi, David W. Speicher, and Ramin Shiekhattar

Genetic, Wistar Institute, Philadelphia, PA 19104

Corresponding Author: shiekhattar{at}wistar.upenn.edu

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.


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