Ctdnep1 and Eps8L2 regulate dorsal actin cables for nuclear positioning during cell migration

Summary Cells actively position their nuclei within the cytoplasm for multiple cellular and physiological functions. Different cell types position their nuclei away from the leading edge to migrate properly. In migrating fibroblasts, nuclear positioning is driven by dorsal actin cables connected to the nuclear envelope by the LINC complex on Transmembrane Actin-associated Nuclear (TAN) lines. How dorsal actin cables are organized to form TAN lines is unknown. Here, we report a role for Ctdnep1/Dullard, a nuclear envelope phosphatase, and the actin regulator Eps8L2, on nuclear positioning. We demonstrate that Ctdnep1 and Eps8L2 directly interact to regulate the formation and thickness of dorsal actin cables required for TAN lines engagement for nuclear positioning. Our work establishes a novel mechanism to locally regulate actin at the nuclear envelope for nuclear positioning.