Contrasting roles of tau and microtubule-associated protein 2 in the vinblastine-induced aggregation of brain tubulin.

R F Ludueña,A Fellous,L Mcmanus,M A Jordan,J Nunez

doi:10.1016/s0021-9258(18)90830-6

Abstract

Two different proteins, tau and microtubule-associated protein 2 (MAP 2), are able to stimulate tubulin polymerization into microtubules in vitro, but it is not certain if both proteins act by the same mechanism. We have examined the effects of tau and MAP 2 on the vinblastine-induced polymerization of tubulin into spiral filaments. In the presence of tau, vinblastine induced extensive aggregation of tubulin as shown by a large increase in turbidity. The increase in turbidity was accompanied by the formation of large numbers of spirals composed of a filament 40-60 A in diameter. The rate and extent of this aggregation into spirals were dependent on the concentrations of tubulin, tau, and vinblastine. Unlike normal microtubule assembly, this type of aggregation was not inhibited by colchicine or podophyllotoxin. In contrast, MAP 2, even at high concentrations, was less effective than tau at promoting the vinblastine-induced increase in turbidity of tubulin. In fact, MAP 2 strongly inhibited the effect of tau. These results indicate that tau and MAP 2 interact differently with the tubulin molecule in the presence of vinblastine and suggest that the two proteins may play different roles in regulating or promoting microtubule assembly. Vinblastine may thus be a useful probe in analyzing the modes of interactions of tau and MAP 2 with tubulin.

Highlights

Tau and microtubule-associated protein 2 (MAP 2), are able to stimulate tubulin polymerization into microtubulesin vitro, but it is not certain if both proteins act by the same mechanism
We have examined the effects of tau and MAP 2 on the vinblastine-inducedpolymerization of tubulin into spiral filaments
The exact mechanism of this stimulation is not clear, but each of these factors can apparently cause tubulin to polymerize into rings or discs which could be assembly intermediates (Murphy and Borisy, 1975; Weingarten et al, 1975).In theabsence of both MAP 2 and tau,low concentrations of pure tubulin from mammalian brain are unable to form microtubules except under nonphysiological conditions, such as in the presence of high concentrations of dimethyl sulfoxide, glycerol, or magnesium

Summary

Introduction

Tau and microtubule-associated protein 2 (MAP 2), are able to stimulate tubulin polymerization into microtubulesin vitro, but it is not certain if both proteins act by the same mechanism. In the presence of tau, vinblastine induced extensive aggregation of tubulin as shown by a large increase in turbidity.

Results

Conclusion