Mitotic phosphorylation of Lamin B1 rod domain by ULK1 and Aurora A/PLK1 promotes spindle function.

Abstract

The coil-coil rod domain that mediates lateral assembly of lamin filaments has been shown by proteomic approaches to undergo phosphorylation, though the function of these modifications remains unknown. Here, we identify serine 210 (S210) within the Lamin B1 rod domain as a mitotic phospho-acceptor residue, regulated by the combined action of the autophagy-activating kinase ULK1 and the mitotic kinases Aurora A and PLK1. Using a phospho-specific antibody, we demonstrate that Lamin B1 phospho-S210 is enriched at the mitotic spindle and interacts with a network of proteins involved in spindle assembly and spindle pole focusing. Preventing S210 phosphorylation increases the number of cells with multipolar or shorter spindles and prolongs mitotic duration. Our findings indicate that mitotic phosphorylation of Lamin B1 at S210 within the rod domain is important for proper spindle organization and focusing during mitosis.