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      An MBoC Favorite: Identification of novel principles of keratin filament turnover in living cells

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      Molecular Biology of the Cell
      The American Society for Cell Biology

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          Abstract

          In celebration of MBoC's first 20 years, members of the Editorial Board, members of the ASCB Council, and others comment on their favorite MBoC papers from the past two decades. This study examines the attributes of keratin intermediate filaments in single, live, nonmotile epithelial cells under steady-state conditions. From their substantive findings, the authors proposed a spatially and temporally defined “keratin cycle” that accounts for the genesis, maturation, and turnover of keratin filaments in the setting of live epithelial cells in culture. I suspect that, just like me, many researchers did not expect that the process of assembly to turnover of keratin filaments would be so vectorial and spatially well-defined, even if it ultimately applies only to a cell culture setting. The “keratin cycle” also provided a conceptual framework from which to examine the relationships among keratin filaments, F-actin, microtubules, and adhesion complexes. The model has been refined since, and several of the predictions it originally generated have been upheld through subsequent experimentation. Finally, this study provided an alternative view of intermediate filament dynamics at steady state, complementing similar efforts from other researchers.

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          Identification of novel principles of keratin filament network turnover in living cells.

          It is generally assumed that turnover of the keratin filament system occurs by exchange of subunits along its entire length throughout the cytoplasm. We now present evidence that a circumscribed submembranous compartment is actually the main site for network replenishment. This conclusion is based on the following observations in living cells synthesizing fluorescent keratin polypeptides: 1) Small keratin granules originate in close proximity to the plasma membrane and move toward the cell center in a continuous motion while elongating into flexible rod-like fragments that fuse with each other and integrate into the peripheral KF network. 2) Recurrence of fluorescence after photobleaching is first seen in the cell periphery where keratin filaments are born that translocate subsequently as part of the network toward the cell center. 3) Partial keratin network reformation after orthovanadate-induced disruption is restricted to a distinct peripheral zone in which either keratin granules or keratin filaments are transiently formed. These findings extend earlier investigations of mitotic cells in which de novo keratin network formation was shown to originate from the cell cortex. Taken together, our results demonstrate that the keratin filament system is not homogeneous but is organized into temporally and spatially distinct subdomains. Furthermore, the cortical localization of the regulatory cues for keratin filament turnover provides an ideal way to adjust the epithelial cytoskeleton to dynamic cellular processes.
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            Author and article information

            Journal
            Mol Biol Cell
            Mol. Biol. Cell
            molbiolcell
            mbc
            Mol. Bio. Cell
            Molecular Biology of the Cell
            The American Society for Cell Biology
            1059-1524
            1939-4586
            15 October 2012
            : 23
            : 20
            : 3926
            Affiliations
            Department of Biochemistry and Molecular Biology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, MD 21205-2185
            Author notes
            1Address correspondence to: Pierre A. Coulombe ( coulombe@ 123456jhsph.edu ).
            Article
            E12-02-0160
            10.1091/mbc.E12-02-0160
            3469508
            23066042
            4d06a9e0-cded-4a7c-b7c2-37457f672a91
            © 2012 Coulombe. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License ( http://creativecommons.org/licenses/by-nc-sa/3.0).

            “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell BD; are registered trademarks of The American Society of Cell Biology.

            History
            Categories
            MBoC 20th Anniversary Favorites

            Molecular biology
            Molecular biology

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