A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus

Cellular asymmetry is critical to metazoan development and the life cycle of many microbes. In Caulobacter, cell cycle progression and the formation of asymmetric daughter cells depend on the polarly-localized histidine kinase CckA. How CckA is regulated and why activity depends on localization are...

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Main Authors: Tsokos, Christos G., Perchuk, Barrett, Laub, Michael T., Tsokos, Christos G., Laub, Michael T
Other Authors: Massachusetts Institute of Technology. Department of Biology
Format: Article
Language:en_US
Published: Elsevier 2014
Online Access:http://hdl.handle.net/1721.1/92029
https://orcid.org/0000-0002-8288-7607
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author Tsokos, Christos G.
Perchuk, Barrett
Laub, Michael T.
Tsokos, Christos G.
Laub, Michael T
author2 Massachusetts Institute of Technology. Department of Biology
author_facet Massachusetts Institute of Technology. Department of Biology
Tsokos, Christos G.
Perchuk, Barrett
Laub, Michael T.
Tsokos, Christos G.
Laub, Michael T
author_sort Tsokos, Christos G.
collection MIT
description Cellular asymmetry is critical to metazoan development and the life cycle of many microbes. In Caulobacter, cell cycle progression and the formation of asymmetric daughter cells depend on the polarly-localized histidine kinase CckA. How CckA is regulated and why activity depends on localization are unknown. Here, we demonstrate that the unorthodox kinase DivL promotes CckA activity and that the phosphorylated regulator DivK inhibits CckA by binding to DivL. Early in the cell cycle, CckA is activated by the dephosphorylation of DivK throughout the cell. However, in later stages, when phosphorylated DivK levels are high, CckA activation relies on polar localization with a DivK phosphatase. Localization thus creates a protected zone for CckA within the cell, without the use of membrane-enclosed compartments. Our results reveal the mechanisms by which CckA is regulated in a cell-type-dependent manner. More generally, our findings reveal how cells exploit subcellular localization to orchestrate sophisticated regulatory processes.
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spelling mit-1721.1/920292022-10-01T19:52:58Z A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus Tsokos, Christos G. Perchuk, Barrett Laub, Michael T. Tsokos, Christos G. Laub, Michael T Massachusetts Institute of Technology. Department of Biology Perchuk, Barrett Laub, Michael T. Tsokos, Christos G. Cellular asymmetry is critical to metazoan development and the life cycle of many microbes. In Caulobacter, cell cycle progression and the formation of asymmetric daughter cells depend on the polarly-localized histidine kinase CckA. How CckA is regulated and why activity depends on localization are unknown. Here, we demonstrate that the unorthodox kinase DivL promotes CckA activity and that the phosphorylated regulator DivK inhibits CckA by binding to DivL. Early in the cell cycle, CckA is activated by the dephosphorylation of DivK throughout the cell. However, in later stages, when phosphorylated DivK levels are high, CckA activation relies on polar localization with a DivK phosphatase. Localization thus creates a protected zone for CckA within the cell, without the use of membrane-enclosed compartments. Our results reveal the mechanisms by which CckA is regulated in a cell-type-dependent manner. More generally, our findings reveal how cells exploit subcellular localization to orchestrate sophisticated regulatory processes. National Institutes of Health (U.S.) (Grant 5R01GM082899) Howard Hughes Medical Institute. Early Career Scientist Program 2014-12-03T19:38:48Z 2014-12-03T19:38:48Z 2011-03 2011-01 Article http://purl.org/eprint/type/JournalArticle 15345807 1878-1551 http://hdl.handle.net/1721.1/92029 Tsokos, Christos G., Barrett S. Perchuk, and Michael T. Laub. “A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter Crescentus.” Developmental Cell 20, no. 3 (March 2011): 329–341. © 2011 Elsevier Inc. https://orcid.org/0000-0002-8288-7607 en_US http://dx.doi.org/10.1016/j.devcel.2011.01.007 Developmental Cell Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Elsevier Elsevier
spellingShingle Tsokos, Christos G.
Perchuk, Barrett
Laub, Michael T.
Tsokos, Christos G.
Laub, Michael T
A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus
title A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus
title_full A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus
title_fullStr A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus
title_full_unstemmed A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus
title_short A Dynamic Complex of Signaling Proteins Uses Polar Localization to Regulate Cell-Fate Asymmetry in Caulobacter crescentus
title_sort dynamic complex of signaling proteins uses polar localization to regulate cell fate asymmetry in caulobacter crescentus
url http://hdl.handle.net/1721.1/92029
https://orcid.org/0000-0002-8288-7607
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