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

Cell growth and division are tightly coordinated to maintain cell size constant during successive cell cycles. In S.pombe the SAD kinase Cdr2 regulates cell size at division and division plane positioning. Cdr2 forms nodes on the medial cortex containing an inhibitory pathway for Wee1, under the negative control of polar gradients of the DYRK kinase Pom1. This pathway involves the SAD kinase Cdr1, a direct inhibitor of Wee1. Cdr2 also interacts with the anillin Mid1 which defines the division plane, and with additional components of medial cortical node, including Blt1, which participate in their mitotic promoting and cytokinetic functions. We show that Cdr2 interaction with Wee1 and Mid1 requires Cdr2 UBA domain necessary for its kinase activity. In contrast, Cdr1 associates with Cdr2 C-terminus composed of basic and KA-1 lipid-binding domains. Mid1 also interacts with Cdr2 C-terminus and may bridge the N- and C-terminal domains while Blt1 associates with the central spacer region. We propose that the association of Cdr2 effectors with different domains may constrain Cdr1 and Wee1 spatially to promote Wee1 inhibition upon Cdr2 kinase activation.