A Phosphorylation Cycle Shapes Gradients of the DYRK Family Kinase Pom1 at the Plasma Membrane

SummaryConcentration gradients regulate many cell biological and developmental processes. In rod-shaped fission yeast cells, polar cortical gradients of the DYRK family kinase Pom1 couple cell length with mitotic commitment by inhibiting a mitotic inducer positioned at midcell. However, how Pom1 gradients are established is unknown. Here, we show that Tea4, which is normally deposited at cell tips by microtubules, is both necessary and, upon ectopic cortical localization, sufficient to recruit Pom1 to the cell cortex. Pom1 then moves laterally at the plasma membrane, which it binds through a basic region exhibiting direct lipid interaction. Pom1 autophosphorylates in this region to lower lipid affinity and promote membrane release. Tea4 triggers Pom1 plasma membrane association by promoting its dephosphorylation through the protein phosphatase 1 Dis2. We propose that local dephosphorylation induces Pom1 membrane association and nucleates a gradient shaped by the opposing actions of lateral diffusion and autophosphorylation-dependent membrane detachment.

Graphical AbstractFigure optionsDownload full-size imageDownload high-quality image (271 K)Download as PowerPoint slideHighlights► Microtubule-deposited Tea4 is necessary and sufficient to nucleate a Pom1 gradient ► Tea4-Dis2 protein phosphatase 1 complex locally dephosphorylates Pom1 ► Unphosphorylated Pom1 kinase directly binds lipids at the plasma membrane ► Pom1 autophosphorylation promotes detachment from the plasma membrane