QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

doi: 10.1242/10.1242/jcs.00096

This Article Figures Only Full Text Full Text (PDF) Movies Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Related articles in JCS Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Strnad, P. Articles by Leube, R. E. Search for Related Content PubMed PubMed Citation Articles by Strnad, P. Articles by Leube, R. E.

Induction of rapid and reversible cytokeratin filament network remodeling by inhibition of tyrosine phosphatases

Department of Anatomy, Johannes Gutenberg-University, Becherweg 13, 55128 Mainz, Germany

^* Author for correspondence (e-mail: leube{at}mail.uni-mainz.de)

Accepted 7 August 2002

The cytokeratin filament network is intrinsically dynamic, continuously exchanging subunits over its entire surface, while conferring structural stability on epithelial cells. However, it is not known how cytokeratin filaments are remodeled in situations where the network is temporarily and spatially restricted. Using the tyrosine phosphatase inhibitor orthovanadate we observed rapid and reversible restructuring in living cells, which may provide the basis for such dynamics. By examining cells stably expressing fluorescent cytokeratin chimeras, we found that cytokeratin filaments were broken down and then formed into granular aggregates within a few minutes of orthovanadate addition. After drug removal, gradual reincorporation of granules into the filament network was observed for aggregates that were either part of residual filaments or stayed in close apposition to remaining filaments. Even when cytokeratin filaments were no longer detectable, granules with low mobility were still able to reestablish a cytokeratin filament network. This process took less than 30 minutes and occurred at multiple foci throughout the cytoplasm without apparent correlation to alterations in the actin- and tubulin-based systems. Interestingly, the short-lived and rather small orthovanadate-induced cytokeratin granules contained the cytoskeletal crosslinker plectin but lacked the cytokeratin-solubilising 14-3-3 proteins. By contrast, the long-lived and larger cytokeratin aggregates generated after treatment with the serine/threonine phosphatase inhibitor okadaic acid were negative for plectin but positive for 14-3-3 proteins. Taken together, our observations in living orthovanadate-treated interphase cells revealed modes of cytokeratin remodeling that qualify as basic mechanisms capable of rapidly adapting the cytokeratin filament cytoskeleton to specific requirements.

Key words: Tyrosine phosphorylation, Keratin, Intermediate filament, Plectin, 14-3-3, Live cell imaging, Green fluorescent protein

Related articles in JCS:

Reversible cytokeratin remodelling

JCS 2002 115: 2104. [Full Text]  

This article has been cited by other articles:

				D. Spazierer, J. Raberger, K. Gross, P. Fuchs, and G. Wiche Stress-induced recruitment of epiplakin to keratin networks increases their resistance to hyperphosphorylation-induced disruption J. Cell Sci., March 15, 2008; 121(6): 825 - 833. [Abstract] [Full Text] [PDF]

				S. Woll, R. Windoffer, and R. E. Leube p38 MAPK-dependent shaping of the keratin cytoskeleton in cultured cells J. Cell Biol., June 21, 2007; 177(5): 795 - 807. [Abstract] [Full Text] [PDF]

				H. A. Long, V. Boczonadi, L. McInroy, M. Goldberg, and A. Maatta Periplakin-dependent re-organisation of keratin cytoskeleton and loss of collective migration in keratin-8-downregulated epithelial sheets J. Cell Sci., December 15, 2006; 119(24): 5147 - 5159. [Abstract] [Full Text] [PDF]

				Q. Zhou, M. Cadrin, H. Herrmann, C.-H. Chen, R. J. Chalkley, A. L. Burlingame, and M. B. Omary Keratin 20 Serine 13 Phosphorylation Is a Stress and Intestinal Goblet Cell Marker J. Biol. Chem., June 16, 2006; 281(24): 16453 - 16461. [Abstract] [Full Text] [PDF]

				R. Windoffer, A. Kolsch, S. Woll, and R. E. Leube Focal adhesions are hotspots for keratin filament precursor formation J. Cell Biol., May 8, 2006; 173(3): 341 - 348. [Abstract] [Full Text] [PDF]

				R. Windoffer, S. Woll, P. Strnad, and R. E. Leube Identification of Novel Principles of Keratin Filament Network Turnover in Living Cells Mol. Biol. Cell, May 1, 2004; 15(5): 2436 - 2448. [Abstract] [Full Text] [PDF]

				N. S. Werner, R. Windoffer, P. Strnad, C. Grund, R. E. Leube, and T. M. Magin Epidermolysis Bullosa Simplex-Type Mutations Alter the Dynamics of the Keratin Cytoskeleton and Reveal a Contribution of Actin to the Transport of Keratin Subunits Mol. Biol. Cell, March 1, 2004; 15(3): 990 - 1002. [Abstract] [Full Text] [PDF]