Stable Pom1 clusters form a glucose-modulated concentration gradient that regulates mitotic entry.

Area of Science:

• Cell biology
• Molecular biology
• Biophysics

Background:

• Cell size control is crucial for cell cycle progression.
• Fission yeast division relies on Cdr2 kinase inhibiting Wee1 at the cell cortex.
• Pom1 kinase forms gradients to inhibit Cdr2, but its precise regulatory role was unclear.

Purpose of the Study:

• To elucidate the spatiotemporal regulation of Pom1 kinase activity in fission yeast.
• To understand how Pom1 interacts with Cdr2 and Wee1 to control cell size.
• To investigate the influence of nutrient availability on cell size control.

Main Methods:

• Live-cell imaging of Pom1 kinase clusters and Cdr2 nodes.
• Quantitative analysis of Pom1 concentration gradients and cluster dynamics.
• Genetic manipulation to assess the roles of polarity landmarks (Tea1, Tea4) and glucose.

Main Results:

• Pom1 kinase forms stable, dynamic oligomeric clusters that sample the cell cortex.
• Pom1 cluster frequency is patterned into a gradient by polarity landmarks Tea1 and Tea4.
• Pom1 clusters colocalize with Cdr2 nodes, creating a glucose-modulated inhibitory threshold for Cdr2 activation, thus controlling entry into mitosis.

Conclusions:

• Pom1-Cdr2-Wee1 interactions occur within multiprotein clusters at the cell cortex.
• This mechanism ensures mitotic entry at a specific cell size, which is tunable by nutrient availability.
• The study reveals a novel layer of spatial and nutrient-dependent regulation in cell size control.