NEUROFIBROMATOSIS TYPE-1 GENE-PRODUCT (NEUROFIBROMIN) ASSOCIATES WITHMICROTUBULES

The neurofibromatosis type 1 (NF1) gene was recently identified by pos itional cloning and found to encode a protein with structural and func tional homology to mammalian and yeast GTPase-activating proteins (GAP s). Using antibodies directed against the NF1 gene product, a protein of approximately 250 kDa was identified and termed neurofibromin. Doub le-indirect immunofluorescent labeling with anti-neurofibromin and ant i-tubulin antibodies demonstrates that neurofibromin associates with c ytoplasmic microtubules. Immunoblotting of microtubule-enriched cytopl asmic fractions, using antibodies generated against neurofibromin, sho ws that neurofibromin copurifies with microtubules. When portions of n eurofibromin are expressed in Sf9 insect cells they associate with pol ymerized microtubules; furthermore, the critical residues for this int eraction reside within the GAP-related domain of neurofibromin. The un expected association of neurofibromin with microtubules suggests that neurofibromin is involved in microtubule-mediated intracellular signal transduction pathways.