Interaction of nerve growth factor with tubulin. Studies on binding and induced polymerization.
The interaction of the nerve growth factor with the neurotubule protein has been studied with the aim of elucidating the nature of the large complexes that they form when incubated together and the factors and control this event. The results show that the binding of nerve growth factor to tubulin is followed by the formation of large structures that, in certain experimental conditions, accelerate the rate of tubulin polymerization to form microtubules or catalyze their assembly in conditions where this process does not occur spontaneously. The formation of large nerve growth factor-tubulin complexes starts to occur only at a molar ratio of 1.0-1.5 NaCL or GTP strongly inhibit this proceed without a detectable effect on NGF binding. Two hypotheses are postulated explain these findings. Firstly, that tubulin has two sites with different affinity for nerve growth factor and the polymerization occurs only when the second NGF molecule has interacted with the microtubule protein. Alternatively, free tubulin in solution is the polymerization by hindering site of tubulin-factor complexes present in solution at a 1.1 molar ratio. In both cases, GTP, Na-+ or H-+ will affect the formation of large unsoluble, tubulin-NGF complexes, by changing their conformation or by decreasing electrostatic interactions.
D000818:Animals; D001665:Binding Sites; D002852:Chromatography, Ion Exchange; D004589:Electrophoresis, Disc; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D008027:Light; D046911:Macromolecular Substances; D008854:Microscopy, Electron; D008870:Microtubules; D008970:Molecular Weight; D009113:Muramidase; D009414:Nerve Growth Factors / Q000302:isolation & purification; D009419:Nerve Tissue Proteins; D011485:Protein Binding; D012542:Scattering, Radiation; D014404:Tubulin / Q000302:isolation & purification; D014747:Vinblastine
D046911:Macromolecular Substances; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D014404:Tubulin; D014747:Vinblastine; D009113:Muramidase