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Modulation of the dynamic instability of tubulin assembly by the microtubule-associated protein tau
D N Drechsel1, A A Hyman, M H Cobb
1Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
Abstract:
Microtubule-associated proteins (MAP), such as tau, modulate the extent and rate of microtubule assembly and play an essential role in morphogenetic processes, such as axonal growth. We have examined the mechanism by which tau affects microtubule polymerization by examining the kinetics of microtubule assembly and disassembly through direct observation of microtubules using dark-field microscopy. Tau increases the rate of polymerization, decreases the rate of transit into the shrinking phase (catastrophe), and inhibits the rate of depolymerization. Tau strongly suppresses the catastrophe rate, and its ability to do so is independent of its ability to increase the elongation rate. Thus, tau generates a partially stable but still dynamic state in microtubules. This state is perturbed by phosphorylation by MAP2 kinase, which affects all three activities by lowering the affinity of tau for the microtubule lattice.
Insights
Tau protein (a microtubule-associated protein) enhances microtubule polymerization and stability by increasing assembly and slowing disassembly. Phosphorylation by MAP2 kinase reduces tau
Area of Science:
- Cell biology
- Neuroscience
- Biochemistry
Background:
- Microtubule-associated proteins (MAPs), including tau, are crucial for microtubule dynamics.
- Tau plays a vital role in morphogenetic processes like axonal growth.
Purpose of the Study:
- To elucidate the mechanism by which tau influences microtubule polymerization and depolymerization kinetics.
- To investigate how tau affects microtubule stability and dynamics.
Main Methods:
- Direct observation of microtubule assembly and disassembly using dark-field microscopy.
- Kinetic analysis of polymerization, catastrophe, and depolymerization rates.
Main Results:
- Tau significantly increases the rate of microtubule polymerization.
- Tau decreases the rate of transition into the shrinking phase (catastrophe) and inhibits depolymerization.
- Tau's suppression of catastrophe rate is independent of its effect on elongation rate, creating a stable yet dynamic state.
Conclusions:
- Tau generates a partially stabilized, dynamic microtubule state essential for cellular processes.
- Phosphorylation by MAP2 kinase perturbs tau's activity by reducing its affinity for microtubules.