Condensation of MATCAP promotes CENP-E-dependent chromosome congression in mitosis.

Abstract

Accurate segregation of mitotic chromosomes requires pre-anaphase alignment driven by microtubule-based motor proteins. Tubulin detyrosination is essential to guide CENP-E-driven chromosome congression in mitosis. However, the mechanisms of action and physiochemical properties of the detyrosinases for decoding CENP-E motility remain elusive. Here we show that microtubule-associated tyrosine carboxypeptidase (MATCAP) undergoes intrinsically disordered region (IDR)-dependent liquid-liquid phase separation (LLPS) on microtubules to constitute the tubulin detyrosination machinery. These biomolecular condensates selectively enrich tubulin and CENP-E, thereby stabilizing kinetochore-microtubule attachments. Real-time imaging of cells expressing LLPS-deficient MATCAP mutants reveals the importance of MATCAP LLPS dynamics in mitotic chromosome alignment. Mechanistically, phase separation of MATCAP spatiotemporally couples tubulin detyrosination with CENP-E motility to ensure a robust chromosome alignment during mitosis. These findings delineate a signaling cascade that integrates phase separation and tubulin detyrosination with mitotic progression for the maintenance of genomic stability.