Neurofibromatosis type 1 gene product (neurofibromin) associates with microtubules.
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 approximately 250 kDa 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 intracellular signal transduction pathways.
Gregory
P E
PE
Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor 48109.
Gutmann
D H
DH
Mitchell
A
A
Park
S
S
Boguski
M
M
Jacks
T
T
Wood
D L
DL
Jove
R
R
Collins
F S
FS
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000818:Animals; D016367:Baculoviridae; D002478:Cells, Cultured; D003001:Cloning, Molecular; D004173:Dipodomys; D005455:Fluorescent Antibody Technique; D020690:GTPase-Activating Proteins; D016514:Genes, Neurofibromatosis 1; D051379:Mice; D008870:Microtubules / Q000378:metabolism*; D008969:Molecular Sequence Data; D009036:Moths; D025542:Neurofibromin 1; D011485:Protein Binding; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D020690:GTPase-Activating Proteins; D025542:Neurofibromin 1; D011506:Proteins