Cleavage of the SUN-domain protein Mps3 at its N-terminus regulates centrosome disjunction in budding yeast meiosis

• Published in: PLoS genetics Vol. 13; no. 6; p. e1006830
• Main Authors: Li, Ping, Jin, Hui, Koch, Bailey A., Abblett, Rebecca L., Han, Xuemei, Yates, John R., Yu, Hong-Guo
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 13.06.2017; Public Library of Science (PLoS)
• Subjects: Biology and Life Sciences; Cell cycle; Cell division; Centrosome; Centrosome - metabolism; Centrosomes; Chromatography; Chromosome Segregation - genetics; Chromosomes; Cleavage; Disjunction; Gene Expression Regulation, Fungal; Homology; Mass spectrometry; Meiosis; Meiosis - genetics; Membrane Proteins - genetics; Microtubules; Microtubules - genetics; N-Terminus; Nuclear Envelope - genetics; Nuclear Proteins - genetics; Nuclei; Observations; Phosphorylation; Physiological aspects; Proteasomes; Protein Domains - genetics; Proteins; Proteomics; Research and Analysis Methods; Saccharomyces cerevisiae - genetics; Saccharomyces cerevisiae Proteins - genetics; Scientific imaging; Serine; Spindle Apparatus - genetics; Sun; Telomere - genetics; Yeast
• ISSN: 1553-7404; 1553-7390; 1553-7404
• DOI: 10.1371/journal.pgen.1006830

Centrosomes organize microtubules and are essential for spindle formation and chromosome segregation during cell division. Duplicated centrosomes are physically linked, but how this linkage is dissolved remains unclear. Yeast centrosomes are tethered by a nuclear-envelope-attached structure called the half-bridge, whose components have mammalian homologues. We report here that cleavage of the half-bridge protein Mps3 promotes accurate centrosome disjunction in budding yeast. Mps3 is a single-pass SUN-domain protein anchored at the inner nuclear membrane and concentrated at the nuclear side of the half-bridge. Using the unique feature in yeast meiosis that centrosomes are linked for hours before their separation, we have revealed that Mps3 is cleaved at its nucleus-localized N-terminal domain, the process of which is regulated by its phosphorylation at serine 70. Cleavage of Mps3 takes place at the yeast centrosome and requires proteasome activity. We show that noncleavable Mps3 (Mps3-nc) inhibits centrosome separation during yeast meiosis. In addition, overexpression of mps3-nc in vegetative yeast cells also inhibits centrosome separation and is lethal. Our findings provide a genetic mechanism for the regulation of SUN-domain protein-mediated activities, including centrosome separation, by irreversible protein cleavage at the nuclear periphery.