CK1-mediated phosphorylation of FAM110A promotes its interaction with mitotic spindle and controls chromosomal alignment

• Published in: EMBO reports Vol. 22; no. 7; pp. e51847 - n/a
• Main Authors: Aquino Perez, Cecilia, Burocziova, Monika, Jenikova, Gabriela, Macurek, Libor
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 05.07.2021; Springer Nature B.V; John Wiley and Sons Inc
• Subjects: Alignment; Anaphase; Casein; casein kinase 1; Casein kinase I; Cell cycle; Cell division; chromosomal alignment; Depletion; EMBO05; EMBO06; Fluorescence; G2 phase; Gene expression; Immunoprecipitation; Kinases; Localization; Mass spectrometry; Mass spectroscopy; Metaphase; Mimicry; Mitosis; Mutants; Phosphorylation; Poles; Spindles; Transformed cells; Tubulin; Ubiquitination; casein kinase 1; chromosomal alignment; mitosis; cell cycle; G2 phase
• ISSN: 1469-221X; 1469-3178; 1469-3178
• DOI: 10.15252/embr.202051847

Progression through the cell cycle is driven by cyclin-dependent kinases that control gene expression, orchestration of mitotic spindle, and cell division. To identify new regulators of the cell cycle, we performed transcriptomic analysis of human non-transformed cells expressing a fluorescent ubiquitination-based cell cycle indicator and identified 701 transcripts differentially expressed in G1 and G2 cells. Family with sequence similarity 110 member A (FAM110A) protein is highly expressed in G2 cells and localized at mitotic spindle and spindle poles during mitosis. Depletion of FAM110A impairs chromosomal alignment, delays metaphase-to-anaphase transition, and affects spindle positioning. Using mass spectrometry and immunoprecipitation, we identified casein kinase I (CK1) in complex with FAM110A during mitosis. CK1 phosphorylates the C-terminal domain of FAM110A in vitro, and inhibition of CK1 reduces phosphorylation of mitotic FAM110A. Wild-type FAM110A, but not the FAM110A-S252-S255A mutant deficient in CK1 phosphorylation, rescues the chromosomal alignment, duration of mitosis, and orientation of the mitotic spindle after depletion of endogenous FAM110A. We propose that CK1 regulates chromosomal alignment by phosphorylating FAM110A and promoting its interaction with mitotic spindle. SYNOPSIS This study reveals that FAM110A is highly expressed in G2 phase. Phosphorylation of FAM110A by Casein kinase 1 controls its recruitment to the spindle pole during mitosis and is needed for correct mitotic progression and normal chromosomal alignment. FAM110A localizes to the proximal spindle and spindle poles and during mitosis. Phosphorylation of FAM110A at S252-255 by Casein kinase 1 delta promotes its interaction with tubulin and localization to the spindle poles. Depletion of FAM110A or inhibition of CK1 lead to chromosomal misalignments and delay progression through mitosis. A phosphorylation-mimicking FAM110A-S252-255E mutant rescues a defect in the chromosomal alignment caused by depletion of CK1. Graphical Abstract This study reveals that FAM110A is highly expressed in G2 phase. Phosphorylation of FAM110A by Casein kinase 1 controls its recruitment to the spindle pole during mitosis and is needed for correct mitotic progression and normal chromosomal alignment.