Dueling kinases regulate cell size at division through the SAD kinase Cdr2

Area of Science:

• Cell biology
• Molecular and developmental biology

Background:

• Cell size control is crucial for proper cell function and relies on integrating cell growth with division.
• In fission yeast, the SAD kinase Cdr2 regulates mitotic entry, but the mechanism of its inhibition by the Pom1 gradient is unclear.

Purpose of the Study:

• To elucidate how the spatial gradient of Pom1 kinase inhibits Cdr2 activity during cell growth.
• To understand the integration of cell size, spatial signaling, and cell cycle progression.

Main Methods:

• In vitro kinase assays
• In vivo cell imaging and genetic analysis in fission yeast
• Phosphorylation site mapping and analysis

Main Results:

• Pom1 inhibits Cdr2 activation by preventing phosphorylation of Thr166 by CaMKK Ssp1.
• Ssp1-mediated phosphorylation of Cdr2 at Thr166 is essential for activating Cdr2 kinase activity and promoting mitotic entry.
• Pom1 phosphorylates Cdr2's C-terminal domain, which reduces Ssp1-mediated activation at Thr166.

Conclusions:

• Pom1's inhibitory action is mediated by preventing Ssp1-dependent Cdr2 activation.
• This study reveals a mechanism linking spatial signaling gradients to cell cycle control for precise cell size regulation.