Keratin filaments of mouse epithelial cells are rapidly affected by epidermal growth factor.

Keski‐Oja, Jorma; Lehto, V.‐P.; Virtanen, Ismo

doi:10.1083/jcb.90.2.537

Cited by 38 publications

(13 citation statements)

References 25 publications

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“…A transitory effect of epidermal growth factor on keratin distribution in mouse embryonic epithelial MMC-E cells causes a short-term keratin filament formation different from the pre-existing condensed keratin normally present in these cells (22). This suggests that the regulation of cytokeratin organization can function in both directions, filamentous --* condensed --> filamentous and condensed --> filamentous -> condensed, and can be influenced by external as well as internal triggering mechanisms.…”

Section: Discussionmentioning

confidence: 99%

Rearrangement of the keratin cytoskeleton after combined treatment with microtubule and microfilament inhibitors.

Knapp¹,

O’Guin²,

Sawyer³

1983

The Journal of Cell Biology

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In addition to containing microtubule and microfilament systems, vertebrate epithelial cells contain an elaborate keratin intermediate-filament cytoskeleton . Little is known about its structural organization or function . Using indirect immunofluorescence microscopy with an antikeratin antiserum probe, we found that destabilization of microtubules and microfilaments with cytostatic drugs induces significant alterations in the cytoskeletal organization of keratin filaments in HeLa and fetal mouse epidermal cells . Keratin filament organization was observed to undergo a rapid (1-2 h) transition from a uniform distribution to an open lattice of keratin fibers stabilized by membrane-associated focal centers . Since addition of any one drug alone did not elicit significant organizational change in the keratin cytoskeleton, we suggest that microfilaments and microtubules have a combined role in maintaining the arrangement of keratin in these cells . Vimentin filaments, the only other intermediatesized filaments found in HeLa cells, did not co-distribute with keratin in untreated or drugtreated cells . These findings offer a new way to approach the study of the dynamics and functional roles of the keratin cytoskeleton in epithelial cells .

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Section: Discussionmentioning

confidence: 99%

Rearrangement of the keratin cytoskeleton after combined treatment with microtubule and microfilament inhibitors.

Knapp¹,

O’Guin²,

Sawyer³

1983

The Journal of Cell Biology

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“…Although the up-regulation of Triton-soluble K17 following EGF stimulation is partly a transcriptional event (data not shown and Ref. 11), EGF also causes rapid changes in keratin filament organization in mouse embryonic epithelial cells (33), rat hepatocytes (34), and human colon cancer cells (35). K6, another type II assembly partner for K17, is expressed in very low amounts in A431 cells (data not shown and Ref.…”

Section: Discussionmentioning

confidence: 99%

Identification of Novel Interaction between Annexin A2 and Keratin 17

Chung

Murray

Eyk

2012

Journal of Biological Chemistry

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Background: Expression of EGFR, K17, and AnxA2 are correlated in cancer settings. Results: AnxA2 and K17 physically interact and undergo reciprocal regulation controlled in part by EGFR signaling. Conclusion: K17 serves as a regulator of the signaling pathway involving AnxA2, whereas AnxA2 regulates K17 stability. Significance: This study demonstrates a novel interaction and reciprocal regulation between AnxA2 and K17.

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“…However, observations have been contradictory and inconclusive, and they have not accounted for network dynamics (e.g., refs. [17][18][19][20]. We therefore wanted to find out whether and how EGF affects the keratin cycle.…”

Section: Measurement Of Keratin Filament Dynamics By Motion and Bulk mentioning

confidence: 99%

Measuring the regulation of keratin filament network dynamics

Moch¹,

Herberich

Aach

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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The organization of the keratin intermediate filament cytoskeleton is closely linked to epithelial function. To study keratin network plasticity and its regulation at different levels, tools are needed to localize and measure local network dynamics. In this paper, we present image analysis methods designed to determine the speed and direction of keratin filament motion and to identify locations of keratin filament polymerization and depolymerization at subcellular resolution. Using these methods, we have analyzed time-lapse fluorescence recordings of fluorescent keratin 13 in human vulva carcinoma-derived A431 cells. The fluorescent keratins integrated into the endogenous keratin cytoskeleton, and thereby served as reliable markers of keratin dynamics. We found that increased times after seeding correlated with down-regulation of inward-directed keratin filament movement. Bulk flow analyses further revealed that keratin filament polymerization in the cell periphery and keratin depolymerization in the more central cytoplasm were both reduced. Treating these cells and other human keratinocyte-derived cells with EGF reversed all these processes within a few minutes, coinciding with increased keratin phosphorylation. These results highlight the value of the newly developed tools for identifying modulators of keratin filament network dynamics and characterizing their mode of action, which, in turn, contributes to understanding the close link between keratin filament network plasticity and epithelial physiology.keratin filament turnover | keratin filament assembly | keratin filament disassembly | growth factor | live cell imaging M echanical properties of cells and tissues are determined by the cytoskeleton, which consists of complex filament networks. Among these networks, the intermediate filament-based network of epithelial cells is the most diverse. More than 50 keratin intermediate filament (KF) polypeptides are expressed in specific combinations in different epithelial cell types. Their importance for epithelial homeostasis is underscored by functions that go beyond cell mechanics as a basis of migration and tissue formation, and contribute to organelle trafficking, protein translation, signaling, immune response, and cell survival (1-4).The continuous inward-directed movement of KFs and the repetitive cycles of KF assembly in the cell periphery and KF disassembly in the more central cytoplasm are striking features of the keratin network in cultured cells (2, 3, 5). These features were determined from time-lapse recordings of fluorescent proteinlabeled keratins, fluorescence recovery after photobleaching (FRAP) experiments, and photoactivation analyses (6, 7). It has been suggested that keratin cycling is needed to establish cell type-specific network architecture and that keratin cycling supports network remodeling while maintaining network integrity, for example, during wound healing and differentiation (2, 5). The regulatory factors affecting keratin cycling and the parts of the cycle subject to regulation ar...

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Keratin filaments of mouse epithelial cells are rapidly affected by epidermal growth factor.

Cited by 38 publications

References 25 publications

Rearrangement of the keratin cytoskeleton after combined treatment with microtubule and microfilament inhibitors.

Rearrangement of the keratin cytoskeleton after combined treatment with microtubule and microfilament inhibitors.

Identification of Novel Interaction between Annexin A2 and Keratin 17

Measuring the regulation of keratin filament network dynamics

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