Gravin-associated kinase signaling networks coordinate γ-tubulin organization at mitotic spindle poles

Abstract

Mitogenic signals that regulate cell division often proceed through multi-enzyme assemblies within defined intracellular compartments. The anchoring protein Gravin restricts the action of mitotic kinases and cell-cycle effectors to defined mitotic structures. In this report we discover that genetic deletion of Gravin disrupts proper accumulation and asymmetric distribution of {gamma}-tubulin during mitosis. We utilize a new precision pharmacology tool, Local Kinase Inhibition (LoKI), to inhibit the Gravin binding partner polo-like kinase 1 (Plk1) at spindle poles. Using a combination of gene-editing approaches, quantitative imaging, and biochemical assays we provide evidence that disruption of local Plk1 signaling underlies the {gamma}-tubulin distribution defects observed with Gravin loss. Our study uncovers a new role for Gravin in coordinating {gamma}-tubulin recruitment during mitosis and illuminates the mechanism by which signaling enzymes regulate this process at a distinct subcellular location.