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DN Drechsel, AA Hyman, MH Cobb and MW Kirschner
Department of Biochemistry and Biophysics, University of California, San Francisco 94143.
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.
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B. L. Goode, M. Chau, P. E. Denis, and S. C. Feinstein Structural and Functional Differences between 3-Repeat and 4-Repeat Tau Isoforms. IMPLICATIONS FOR NORMAL TAU FUNCTION AND THE ONSET OF NEURODEGENERATIVE DISEASE J. Biol. Chem., December 1, 2000; 275(49): 38182 - 38189. [Abstract] [Full Text] [PDF]
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L. Romberg, M. Simon, and H. P. Erickson Polymerization of FtsZ, a Bacterial Homolog of Tubulin. IS ASSEMBLY COOPERATIVE? J. Biol. Chem., April 6, 2001; 276(15): 11743 - 11753. [Abstract] [Full Text] [PDF]
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M. A. Utton, G. M. Gibb, I. D. J. Burdett, B. H. Anderton, and A. Vandecandelaere Functional Differences of Tau Isoforms Containing 3 or 4 C-terminal Repeat Regions and the Influence of Oxidative Stress J. Biol. Chem., August 31, 2001; 276(36): 34288 - 34297. [Abstract] [Full Text] [PDF]
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M. Rapoport, H. N. Dawson, L. I. Binder, M. P. Vitek, and A. Ferreira Tau is essential to beta -amyloid-induced neurotoxicity PNAS, April 30, 2002; 99(9): 6364 - 6369. [Abstract] [Full Text] [PDF]
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