Journal of Cell Science, Vol 107, Issue 1 135-143, Copyright © 1994 by Company of Biologists

JOURNAL ARTICLES

Tau confers drug stability but not cold stability to microtubules in living cells

PW Baas, TP Pienkowski, KA Cimbalnik, K Toyama, S Bakalis, FJ Ahmad and KS Kosik
Department of Anatomy, University of Wisconsin Medical School, Madison 53706.

We previously defined two classes of microtubule polymer in the axons of cultured sympathetic neurons that differ in their sensitivity to nocodazole by roughly 35-fold (Baas and Black (1990) J. Cell Biol. 111, 495-509). Here we demonstrate that virtually all of the microtubule polymer in these axons, including the drug-labile polymer, is stable to cold. What factors account for the unique stability properties of axonal microtubules? In the present study, we have focused on the role of tau, a microtubule-associated protein that is highly enriched in the axon, in determining the stability of microtubules to nocodazole and/or cold in living cells. We used a baculovirus vector to express very high levels of tau in insect ovarian Sf9 cells. The cells respond by extending processes that contain dense bundles of microtubules (Knops et al. (1991) J. Cell Biol. 114, 725-734). Cells induced to express tau were treated with either cold or 2 micrograms/ml nocodazole for times ranging from 5 minutes to 6 hours. The results with each treatment were very different from one another. Virtually all of the polymer was depolymerized within the first 30 minutes in cold, while little or no microtubule depolymerization was detected even after 6 hours in nocodazole. Based on these results, we conclude that tau is almost certainly a factor in conferring drug stability to axonal microtubules, but that factors other than or in addition to tau are required to confer cold stability.

This article has been cited by other articles:

				A. M. Jaramillo, T. T. Weil, J. Goodhouse, E. R. Gavis, and T. Schupbach The dynamics of fluorescently labeled endogenous gurken mRNA in Drosophila J. Cell Sci., March 15, 2008; 121(6): 887 - 894. [Abstract] [Full Text] [PDF]

				Z. Hou, Q. Li, L. He, H.-Y. Lim, X. Fu, N. S. Cheung, D. X. Qi, and R. Z. Qi Microtubule Association of the Neuronal p35 Activator of Cdk5 J. Biol. Chem., June 29, 2007; 282(26): 18666 - 18670. [Abstract] [Full Text] [PDF]

				J. Ferralli, J. Ashby, M. Fasler, V. Boyko, and M. Heinlein Disruption of Microtubule Organization and Centrosome Function by Expression of Tobacco Mosaic Virus Movement Protein. J. Virol., June 1, 2006; 80(12): 5807 - 5821. [Abstract] [Full Text] [PDF]

				L. Liu, A. Vo, and W. L. McKeehan Specificity of the Methylation-Suppressed A Isoform of Candidate Tumor Suppressor RASSF1 for Microtubule Hyperstabilization Is Determined by Cell Death Inducer C19ORF5 Cancer Res., March 1, 2005; 65(5): 1830 - 1838. [Abstract] [Full Text] [PDF]

				J. AVILA, J. J. LUCAS, M. PEREZ, and F. HERNANDEZ Role of Tau Protein in Both Physiological and Pathological Conditions Physiol Rev, April 1, 2004; 84(2): 361 - 384. [Abstract] [Full Text] [PDF]

				A. C. B. Lim, S.-Y. Tiu, Q. Li, and R. Z. Qi Direct Regulation of Microtubule Dynamics by Protein Kinase CK2 J. Biol. Chem., February 6, 2004; 279(6): 4433 - 4439. [Abstract] [Full Text] [PDF]

				A. Andrieux, P. A. Salin, M. Vernet, P. Kujala, J. Baratier, S. Gory-Faure, C. Bosc, H. Pointu, D. Proietto, A. Schweitzer, et al. The suppression of brain cold-stable microtubules in mice induces synaptic defects associated with neuroleptic-sensitive behavioral disorders Genes & Dev., September 15, 2002; 16(18): 2350 - 2364. [Abstract] [Full Text] [PDF]

				O. Krylova, M. J. Messenger, and P. C. Salinas Dishevelled-1 Regulates Microtubule Stability: A New Function Mediated by Glycogen Synthase Kinase-3{beta} J. Cell Biol., October 3, 2000; 151(1): 83 - 94. [Abstract] [Full Text] [PDF]

				J. Biernat and E.-M. Mandelkow The Development of Cell Processes Induced by tau Protein Requires Phosphorylation of Serine 262 and 356 in the Repeat Domain and Is Inhibited by Phosphorylation in the Proline-rich Domains Mol. Biol. Cell, March 1, 1999; 10(3): 727 - 740. [Abstract] [Full Text]

				L. Guillaud, C. Bosc, A. Fourest-Lieuvin, E. Denarier, F. Pirollet, L. Lafanechere, and D. Job STOP Proteins are Responsible for the High Degree of Microtubule Stabilization Observed in Neuronal Cells J. Cell Biol., July 13, 1998; 142(1): 167 - 179. [Abstract] [Full Text] [PDF]

				E. Denarier, A. Fourest-Lieuvin, C. Bosc, F. Pirollet, A. Chapel, R. L. Margolis, and D. Job Nonneuronal isoforms of STOP protein are responsible for microtubule cold stability in mammalian fibroblasts PNAS, May 26, 1998; 95(11): 6055 - 6060. [Abstract] [Full Text] [PDF]

				I. R. Nabi, G. Guay, and D. Simard AMF-R Tubules Concentrate in a Pericentriolar Microtubule Domain After MSV Transformation of Epithelial MDCK Cells J. Histochem. Cytochem., October 1, 1997; 45(10): 1351 - 1364. [Abstract] [Full Text] [PDF]

				U Preuss, J Biernat, E. Mandelkow, and E Mandelkow The 'jaws' model of tau-microtubule interaction examined in CHO cells J. Cell Sci., January 3, 1997; 110(6): 789 - 800. [Abstract] [PDF]

				M. Kempf, A. Clement, A. Faissner, G. Lee, and R. Brandt Tau Binds to the Distal Axon Early in Development of Polarity in a Microtubule- and Microfilament-Dependent Manner J. Neurosci., September 15, 1996; 16(18): 5583 - 5592. [Abstract] [Full Text] [PDF]

				M. M. Black, T. Slaughter, S. Moshiach, M. Obrocka, and I. Fischer Tau Is Enriched on Dynamic Microtubules in the Distal Region of Growing Axons J. Neurosci., June 1, 1996; 16(11): 3601 - 3619. [Abstract] [Full Text] [PDF]

				F. Ahmad and P. Baas Microtubules released from the neuronal centrosome are transported into the axon J. Cell Sci., January 8, 1995; 108(8): 2761 - 2769. [Abstract] [PDF]

				C. Bosc, R. Frank, E. Denarier, M. Ronjat, A. Schweitzer, J. Wehland, and D. Job Identification of Novel Bifunctional Calmodulin-binding and Microtubule-stabilizing Motifs in STOP Proteins J. Biol. Chem., August 10, 2001; 276(33): 30904 - 30913. [Abstract] [Full Text] [PDF]