Somatic Cell and Molecular Genetics

, Volume 19, Issue 3, pp 265–274 | Cite as

Neurofibromatosis type 1 gene product (neurofibromin) associates with microtubules

  • Paula E. Gregory
  • David H. Gutmann
  • Anna Mitchell
  • Soochul Park
  • Mark Boguski
  • Tyler Jacks
  • Deborah L. Wood
  • Richard Jove
  • Francis S. Collins
Article

Abstract

The neurofibromatosis type 1 (NF1) gene was recently identified by positional cloning and found to encode a protein with structural and functional homology to mammalian and yeast GTPase-activating proteins (GAPs). Using antibodies directed against the NF1 gene product, a protein of ∼250kDa was identified and termed neurofibromin. Double-indirect immunofluorescent labeling with anti-neurofibromin and anti-tubulin antibodies demonstrates that neurofibromin associates with cytoplasmic microtubules. Immunoblotting of microtubule-enriched cytoplasmic fractions, using antibodies generated against neurofibromin, shows that neurofibromin copurifies with microtubules. When portions of neurofibromin are expressed in Sf9 insect cells they associate with polymerized microtubules; furthermore, the critical residues for this interaction reside within the GAP-related domain of neurofibromin. The unexpected association of neurofibromin with microtubules suggests that neurofibromin is involved in microtubule-mediated intracellullar signal transduction pathways.

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Copyright information

© Plenum Publishing Corporation 1993

Authors and Affiliations

  • Paula E. Gregory
    • 1
  • David H. Gutmann
    • 1
  • Anna Mitchell
    • 1
  • Soochul Park
    • 1
  • Mark Boguski
    • 2
  • Tyler Jacks
    • 3
  • Deborah L. Wood
    • 1
  • Richard Jove
    • 1
  • Francis S. Collins
    • 1
  1. 1.The Departments of Internal Medicine, Human Genetics, Neurology and Microbiology and ImmunologyThe University of Michigan Medical Center and The Howard Hughes Medical Institute, The University of MichiganAnn Arbor
  2. 2.National Center for Biotechnology InformationNIHBethesda
  3. 3.Center for Cancer ResearchMassachusetts Institute of TechnologyCambridge

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