How cells determine the number of polarity sites
Jian-Geng Chiou1, Kyle D Moran1, Daniel J Lew1
1Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, United States.
Abstract:
The diversity of cell morphologies arises, in part, through regulation of cell polarity by Rho-family GTPases. A poorly understood but fundamental question concerns the regulatory mechanisms by which different cells generate different numbers of polarity sites. Mass-conserved activator-substrate (MCAS) models that describe polarity circuits develop multiple initial polarity sites, but then those sites engage in competition, leaving a single winner. Theoretical analyses predicted that competition would slow dramatically as GTPase concentrations at different polarity sites increase toward a 'saturation point', allowing polarity sites to coexist. Here, we test this prediction using budding yeast cells, and confirm that increasing the amount of key polarity proteins results in multiple polarity sites and simultaneous budding. Further, we elucidate a novel design principle whereby cells can switch from competition to equalization among polarity sites. These findings provide insight into how cells with diverse morphologies may determine the number of polarity sites.
Insights
Cells can control their shape by regulating polarity sites. Increasing key protein amounts leads to multiple sites and simultaneous budding, revealing a new cellular design principle for diverse morphologies.
Area of Science:
- Cell biology
- Biophysics
- Systems biology
Background:
- Cell morphology diversity is partly regulated by Rho-family GTPases controlling cell polarity.
- The mechanisms by which cells generate varying numbers of polarity sites remain poorly understood.
- Existing Mass-Conserved Activator-Substrate (MCAS) models predict competition among initial polarity sites, resulting in a single dominant site.
Purpose of the Study:
- To investigate the regulatory mechanisms controlling the number of cell polarity sites.
- To test theoretical predictions regarding the saturation point of GTPase concentrations and polarity site coexistence.
- To elucidate novel design principles governing cell polarity site dynamics.
Main Methods:
- Utilizing budding yeast as a model organism.
- Experimentally manipulating the concentrations of key polarity proteins.
- Observing and quantifying the number and behavior of polarity sites.
- Analyzing cell morphology and budding patterns.
Main Results:
- Confirmed theoretical predictions that increased GTPase concentrations slow competition, allowing multiple polarity sites to coexist.
- Demonstrated that higher amounts of key polarity proteins lead to the formation of multiple polarity sites.
- Observed simultaneous budding events in yeast cells with increased polarity sites.
- Identified a novel design principle enabling cells to switch from polarity site competition to equalization.
Conclusions:
- Cellular morphology diversity is influenced by the regulation of cell polarity sites.
- Increased concentrations of polarity proteins can lead to the coexistence of multiple polarity sites.
- Cells possess mechanisms to switch between competitive and equalizing dynamics for polarity sites.
- Findings offer insights into how cells determine the number of polarity sites, contributing to diverse morphologies.
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