Cell fate control by spatiotemporally regulated signaling pathways
Abstract/Contents
- Abstract
- Cells must coordinate their behaviors to occur at the correct time and place. Asymmetric cell division, which underlies cellular differentiation across the kingdoms of life, presents a major coordination challenge. Cell fate signaling proteins must respond to cell cycle progression cues, interpreting these signals in the context of their subcellular location. We studied how the bacterium Caulobacter crescentus, a model organism for the study of asymmetric division, coordinates cell polarity, differentiation, and DNA replication. Caulobacter couples these processes through spatiotemporal control of the phosphorylation state of a master regulator, CtrA. Beginning with an investigation of the ordered assembly of a G1/S signaling complex that downregulates the level of active CtrA~P, we find that disruptions to the expression level or localization of this G1/S complex creates major cell polarity aberrations. We further investigate how CtrA becomes reactivated by a multi-sensor histidine kinase, CckA, in late S-phase. CckA switches between kinase and phosphatase activity towards CtrA in response to multiple spatially controlled upstream signals. CckA detects these signals, which include its own membrane surface density, the second messenger c-di-GMP, and a pseudokinase, DivL, through distinct sensory PAS domains. Our study of CckA's signal transduction illustrates how multi-sensor kinases enable complex bacterial decision making based on an array of spatially and temporally oscillating inputs.
Description
| Type of resource | text |
|---|---|
| Form | electronic; electronic resource; remote |
| Extent | 1 online resource. |
| Publication date | 2017 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Associated with | Mann, Thomas H |
|---|---|
| Associated with | Stanford University, Department of Biochemistry. |
| Primary advisor | Shapiro, Lucy |
| Primary advisor | Straight, Aaron, 1966- |
| Thesis advisor | Shapiro, Lucy |
| Thesis advisor | Straight, Aaron, 1966- |
| Thesis advisor | Long, Sharon |
| Thesis advisor | Spudich, James A |
| Advisor | Long, Sharon |
| Advisor | Spudich, James A |
Subjects
| Genre | Theses |
|---|
Bibliographic information
| Statement of responsibility | Thomas H. Mann. |
|---|---|
| Note | Submitted to the Department of Biochemistry. |
| Thesis | Thesis (Ph.D.)--Stanford University, 2017. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2017 by Thomas Holladay Mann
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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