Molecular control of the Wee1 regulatory pathway by the SAD kinase Cdr2

Area of Science:

• Cell biology
• Molecular and developmental biology

Background:

• Cell growth and division must be coordinated to maintain constant cell size.
• In Schizosaccharomyces pombe, the SAD kinase Cdr2 is crucial for regulating cell division size and plane positioning.
• Cdr2 forms medial cortical nodes involved in cell division regulation.

Purpose of the Study:

• To investigate the specific domains of Cdr2 involved in its interactions with key regulatory proteins.
• To elucidate how Cdr2's interactions contribute to the spatial organization of the Wee1 inhibitory pathway.
• To understand the mechanism by which Cdr2 regulates cell division in fission yeast.

Main Methods:

• Analysis of protein-protein interactions between Cdr2 and its binding partners (Wee1, Mid1, Cdr1, Blt1).
• Domain mapping to identify specific regions of Cdr2 responsible for these interactions.
• Investigating the role of Cdr2's UBA domain, kinase activity, and C-terminal domains in regulating cell division.

Main Results:

• The UBA domain of Cdr2 is essential for its interaction with Wee1 and Mid1, and is required for Cdr2's kinase activity.
• Cdr1 binds to the C-terminus of Cdr2, while Blt1 associates with the central spacer region.
• Mid1 also interacts with the C-terminus of Cdr2, potentially bridging different domains of Cdr2.

Conclusions:

• Cdr2 utilizes distinct domains to interact with its effectors, including Wee1, Mid1, Cdr1, and Blt1.
• This domain-specific binding spatially organizes the inhibitory pathway components, likely constraining Cdr1 and Wee1.
• Spatial organization mediated by Cdr2 promotes Wee1 inhibition upon Cdr2 kinase activation, ensuring proper cell division.