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Mitogenic signals that regulate cell division often proceed through multienzyme 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 γ-tubulin during mitosis. We utilize a new precision pharmacology tool, Local Kinase Inhibition, to inhibit the Gravin binding partner polo-like kinase 1 at spindle poles. Using a combination of gene-editing approaches, quantitative imaging, and biochemical assays, we provide evidence that disruption of local polo-like kinase 1 signaling underlies the γ-tubulin distribution defects observed with Gravin loss. Our study uncovers a new role for Gravin in coordinating γ-tubulin recruitment during mitosis and illuminates the mechanism by which signaling enzymes regulate this process at a distinct subcellular location. © 2020 Bucko et al.

Citation

Paula J Bucko, Irvin Garcia, Ridhima Manocha, Akansha Bhat, Linda Wordeman, John D Scott. Gravin-associated kinase signaling networks coordinate γ-tubulin organization at mitotic spindle poles. The Journal of biological chemistry. 2020 Oct 02;295(40):13784-13797

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PMID: 32732289

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