biostudies-literatureUnknown301(1)Yasutake RJapan Society for the Promotion of ScienceEphexin proteins are guanine nucleotide exchange factors for the Rho GTPases. We reported that Ephexin4 regulates M-phase progression downstream of phosphorylated EphA2, a receptor-type tyrosine kinase, through RhoG activation; however, the regulation of Ephexin4 during M phase remains unknown. In this study, a novel Ephexin4 phosphorylation site was identified at Ser41, exclusively in M phase. Ephexin4 knockdown prolonged the duration of M phase by activating the spindle assembly checkpoint, at which BubR1 was localized at the kinetochores of the misaligned chromosomes. This delay was alleviated by re-expression of wild-type, but not S41A Ephexin4. The Ephexin4 knockdown caused chromosome misalignment and reduced the RhoG localization to the plasma membrane. These phenotypes were rescued The Journal of biological chemistry108084https://www.ebi.ac.uk/biostudies/studies/S-EPMC11758948biostudies-literaturePhosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.PMC11758948Kuwajima HYasutake RNakayama YSaito YTanaka JYuki RfalsePhosphorylation of Ephexin4 at Ser-41 contributes to chromosome alignment via RhoG activation in cell division.Ephexin proteins are guanine nucleotide exchange factors for the Rho GTPases. We reported that Ephexin4 regulates M-phase progression downstream of phosphorylated EphA2, a receptor-type tyrosine kinase, through RhoG activation; however, the regulation of Ephexin4 during M phase remains unknown. In this study, a novel Ephexin4 phosphorylation site was identified at Ser41, exclusively in M phase. Ephexin4 knockdown prolonged the duration of M phase by activating the spindle assembly checkpoint, at which BubR1 was localized at the kinetochores of the misaligned chromosomes. This delay was alleviated by re-expression of wild-type, but not S41A Ephexin4. The Ephexin4 knockdown caused chromosome misalignment and reduced the RhoG localization to the plasma membrane. These phenotypes were rescued 2025-01-01T00:00:00Z2025 Jan2025-04-03T23:36:49.015Z2025-04-03T23:36:49.015ZS-EPMC117589483967571310.1016/j.jbc.2024.108084