Cdc42 mobility and membrane flows regulate fission yeast cell shape and survival.

Area of Science:

• Cell Biology
• Biophysics
• Systems Biology

Background:

• Cdc42 GTPase is a key regulator of cell polarity.
• Membrane-associated proteins play critical roles in cellular processes.
• Exocytosis and endocytosis contribute to membrane dynamics.

Purpose of the Study:

• To investigate the role of membrane flows in Cdc42-driven cell polarization.
• To model the interplay between Cdc42 activity, membrane flow, and protein mobility.
• To experimentally validate model predictions using modified Cdc42 alleles in yeast.

Main Methods:

• Developed a reaction-diffusion particle model for Cdc42 activation, hydrolysis, and flow-induced displacement.
• Engineered Schizosaccharomyces pombe strains with altered Cdc42 mobility by modifying its prenylation site.
• Assessed cell viability and polarization in engineered yeast strains and deletion mutants.

Main Results:

• Model predicted that flow-induced depletion of low-mobility GTPase-activating proteins (GAPs) promotes polarization.
• Experimentally created Cdc42 alleles with decreased mobility and increased flow-coupling.
• Observed that reduced Cdc42 mobility impaired polarization and viability, consistent with model predictions.
• Deletion of Cdc42 GAPs restored viability but compromised polarization in low-mobility Cdc42 mutants.

Conclusions:

• Membrane flows are integral to Cdc42-driven pattern formation and cell polarization.
• Cdc42-GTP turnover rate must exceed the surface rate for effective pattern formation.
• The interplay between protein mobility, membrane flow, and GTPase activity governs cell polarity.