Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011.
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| Format: | Thesis |
| Language: | eng |
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Massachusetts Institute of Technology
2012
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| Online Access: | http://hdl.handle.net/1721.1/68430 |
| _version_ | 1811083647157010432 |
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| author | Tsokos, Christos G |
| author2 | Michael T. Laub. |
| author_facet | Michael T. Laub. Tsokos, Christos G |
| author_sort | Tsokos, Christos G |
| collection | MIT |
| description | Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011. |
| first_indexed | 2024-09-23T12:36:30Z |
| format | Thesis |
| id | mit-1721.1/68430 |
| institution | Massachusetts Institute of Technology |
| language | eng |
| last_indexed | 2024-09-23T12:36:30Z |
| publishDate | 2012 |
| publisher | Massachusetts Institute of Technology |
| record_format | dspace |
| spelling | mit-1721.1/684302019-04-12T12:17:58Z Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins Tsokos, Christos G Michael T. Laub. Massachusetts Institute of Technology. Dept. of Biology. Massachusetts Institute of Technology. Dept. of Biology. Biology. Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2011. Cataloged from PDF version of thesis. Includes bibliographical references. Cellular asymmetry is critical to the generation of complexity in both metazoans and many microbes. However, several molecular mechanisms responsible for translating asymmetry into differential cell fates remain unknown. Caulobacter crescentus provides an excellent model to study this process because every division is asymmetric. One daughter cell, the stalked cell, is sessile and commits immediately to S phase. The other daughter, the swarmer cell, is motile and locked in G1. Cellular differentiation requires asymmetric distribution or activation of regulatory factors. In Caulobacter, the master cell cycle regulator CtrA is selectively activated in swarmer cells, deactivated in stalked cells, and reactivated in predivisional cells. CtrA controls DNA replication, polar morphogenesis and cell division, and its cell-type and cell cycle-specific regulation is essential to the life cycle of Caulobacter. In swarmer cells, activated CtrA binds to the origin of replication and holds cells in G1. In stalked cells, CtrA deactivation allows for the initiation of DNA replication. Finally, in predivisional cells, CtrA is reactivated and acts as a transcription factor for >100 genes including those involved in polar morphogenesis and cell division. CtrA regulation is determined by the polarly localized histidine kinase CckA, but how CckA is differentially regulated in each cell type and why activity depends on localization are unknown. This thesis demonstrates that the unorthodox kinase DivL promotes CckA activity and that the phosphorylated regulator DivK inhibits CckA by binding to DivL. Differential cellular fates are achieved by regulating the phosphorylation state of DivK. In swarmer cells, DivK is dephosphorylated, thereby activating CckA and arresting the cells in G1. In stalked cells, phosphorylated DivK inactivates CckA, thus allowing for DNA replication initiation. Paradoxically, in predivisional cells, while phosphorylated DivK levels remain high, CckA is reactivated to initiate cellular division and morphogenesis. CckA activation in this cell type 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. These results reveal the mechanisms by which CckA is regulated in a cell-type-dependent manner. More generally, these findings reveal how cells exploit subcellular localization to orchestrate sophisticated regulation. by Christos G. Tsokos. Ph.D. 2012-01-12T19:27:03Z 2012-01-12T19:27:03Z 2011 2011 Thesis http://hdl.handle.net/1721.1/68430 768828328 eng M.I.T. theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission. See provided URL for inquiries about permission. http://dspace.mit.edu/handle/1721.1/7582 127 p. application/pdf Massachusetts Institute of Technology |
| spellingShingle | Biology. Tsokos, Christos G Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins |
| title | Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins |
| title_full | Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins |
| title_fullStr | Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins |
| title_full_unstemmed | Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins |
| title_short | Regulation of cell fate asymmetry in Caulobacter crescentus by a complex of two component signaling proteins |
| title_sort | regulation of cell fate asymmetry in caulobacter crescentus by a complex of two component signaling proteins |
| topic | Biology. |
| url | http://hdl.handle.net/1721.1/68430 |
| work_keys_str_mv | AT tsokoschristosg regulationofcellfateasymmetryincaulobactercrescentusbyacomplexoftwocomponentsignalingproteins |