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  A molecular mechanotransduction pathway regulates collective migration of epithelial cells

Das, T., Safferling, K., Rausch, S., Grabe, N., Böhm, H., & Spatz, J. P. (2015). A molecular mechanotransduction pathway regulates collective migration of epithelial cells. Nature Cell Biology, 17(3), 276-287. doi:10.1038/ncb3115.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0025-6C80-8 Version Permalink: http://hdl.handle.net/11858/00-001M-0000-002E-7CED-D
Genre: Journal Article

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NatCellBiol_17_2015_276.pdf (Any fulltext), 7MB
 
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 Creators:
Das, Tamal1, 2, Author              
Safferling, Kai, Author
Rausch, Sebastian, Author              
Grabe, Niels, Author
Böhm, Heike1, 2, Author              
Spatz, Joachim P.1, 2, Author              
Affiliations:
1Cellular Biophysics, Max Planck Institute for Medical Research, Max Planck Society, ou_2364731              
2Biophysical Chemistry, Institute of Physical Chemistry, University of Heidelberg, 69120 Heidelberg, Germany, ou_persistent22              

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 Abstract: Collective movement of epithelial cells drives essential multicellular organization during various fundamental physiological processes encompassing embryonic morphogenesis, cancer and wound healing. Yet the molecular mechanism that ensures the coordinated movement of many cells remains elusive. Here we show that a tumour suppressor protein, merlin, coordinates collective migration of tens of cells, by acting as a mechanochemical transducer. In a stationary epithelial monolayer and also in three-dimensional human skin, merlin localizes to cortical cell-cell junctions. During migration initiation, a fraction of cortical merlin relocalizes to the cytoplasm. This relocalization is triggered by the intercellular pulling force of the leading cell and depends on the actomyosin-based cell contractility. Then in migrating cells, taking its cue from the intercellular pulling forces, which show long-distance ordering, merlin coordinates polarized Rac1 activation and lamellipodium formation on the multicellular length scale. Together, these results provide a distinct molecular mechanism linking intercellular forces to collective cell movements in migrating epithelia.

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Language(s): eng - English
 Dates: 2014-07-292015-01-162015-02-232015-03-01
 Publication Status: Published in print
 Pages: 27
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 Table of Contents: -
 Rev. Method: Peer
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Title: Nature Cell Biology
  Other : 'Nat. Cell Biol.'
Source Genre: Journal
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Publ. Info: London : Macmillan Magazines Ltd.
Pages: - Volume / Issue: 17 (3) Sequence Number: - Start / End Page: 276 - 287 Identifier: ISSN: 1465-7392
CoNE: /journals/resource/954925625310