{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T12:19:28Z","timestamp":1784290768108,"version":"3.55.0"},"reference-count":54,"publisher":"American Society for Cell Biology (ASCB)","issue":"3","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2004,3]]},"abstract":"<jats:p>Dominant keratin mutations cause epidermolysis bullosa simplex by transforming keratin (K) filaments into aggregates. As a first step toward understanding the properties of mutant keratins in vivo, we stably transfected epithelial cells with an enhanced yellow fluorescent protein-tagged K14R<jats:sub>125<\/jats:sub>C mutant. K14R<jats:sub>125<\/jats:sub>C became localized as aggregates in the cell periphery and incorporated into perinuclear keratin filaments. Unexpectedly, keratin aggregates were in dynamic equilibrium with soluble subunits at a half-life time of &lt;15 min, whereas filaments were extremely static. Therefore, this dominant-negative mutation acts by altering cytoskeletal dynamics and solubility. Unlike previously postulated, the dominance of mutations is limited and strictly depends on the ratio of mutant to wild-type protein. In support, K14R<jats:sub>125<\/jats:sub>C-specific RNA interference experiments resulted in a rapid disintegration of aggregates and restored normal filaments. Most importantly, live cell inhibitor studies revealed that the granules are transported from the cell periphery inwards in an actin-, but not microtubule-based manner. The peripheral granule zone may define a region in which keratin precursors are incorporated into existing filaments. Collectively, our data have uncovered the transient nature of keratin aggregates in cells and offer a rationale for the treatment of epidermolysis bullosa simplex by using short interfering RNAs.<\/jats:p>","DOI":"10.1091\/mbc.e03-09-0687","type":"journal-article","created":{"date-parts":[[2003,12,16]],"date-time":"2003-12-16T01:13:32Z","timestamp":1071537212000},"page":"990-1002","source":"Crossref","is-referenced-by-count":89,"title":["Epidermolysis Bullosa Simplex-Type Mutations Alter the Dynamics of the Keratin Cytoskeleton and Reveal a Contribution of Actin to the Transport of Keratin Subunits"],"prefix":"10.1091","volume":"15","author":[{"given":"Nicola Susann","family":"Werner","sequence":"first","affiliation":[{"name":"Institut fuer Physiologische Chemie, Abteilung fuer Zellbiochemie, Universitaetsklinikum Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Reinhard","family":"Windoffer","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Johannes Gutenberg-University, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel","family":"Strnad","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Johannes Gutenberg-University, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christine","family":"Grund","sequence":"additional","affiliation":[{"name":"Division of Cell Biology, German Cancer Research Center, 69120 Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rudolf Eberhard","family":"Leube","sequence":"additional","affiliation":[{"name":"Department of Anatomy, Johannes Gutenberg-University, D-55128 Mainz, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas Michael","family":"Magin","sequence":"additional","affiliation":[{"name":"Institut fuer Physiologische Chemie, Abteilung fuer Zellbiochemie, Universitaetsklinikum Bonn, 53115 Bonn, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1076","reference":[{"key":"REF1","doi-asserted-by":"crossref","unstructured":"Amann, K.J., and Pollard, T.D. 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