The 14-3-3 protein Bmh1 functions in the spindle position checkpoint by breaking Bfa1 asymmetry at yeast centrosomes.
In addition to their well-known role in microtubule organization, centrosomes function as signaling platforms and regulate cell cycle events. An important example of such a function is the spindle position checkpoint (SPOC) of budding yeast. SPOC is a surveillance mechanism that ensures alignment of the mitotic spindle along the cell polarity axis. Upon spindle misalignment, phosphorylation of the SPOC component Bfa1 by Kin4 kinase engages the SPOC by changing the centrosome localization of Bfa1 from asymmetric (one centrosome) to symmetric (both centrosomes). Here we show that, unexpectedly, Kin4 alone is unable to break Bfa1 asymmetry at yeast centrosomes. Instead, phosphorylation of Bfa1 by Kin4 creates a docking site on Bfa1 for the 14-3-3 family protein Bmh1, which in turn weakens Bfa1-centrosome association and promotes symmetric Bfa1 localization. Consistently, BMH1-null cells are SPOC deficient. Our work thus identifies Bmh1 as a new SPOC component and refines the molecular mechanism that breaks Bfa1 centrosome asymmetry upon SPOC activation.
Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg 69120, Germany.
Ayse Koca
AK
Caydasi
Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg 69120, Germany.
Yagmur
Y
Micoogullari
Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg 69120, Germany.
Bahtiyar
B
Kurtulmus
Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg 69120, Germany.
Saravanan
S
Palani
Molecular Biology of Centrosomes and Cilia, German Cancer Research Center, DKFZ-ZMBH Alliance, Heidelberg 69120, Germany g.pereira@dkfz.de.
Gislene
G
Pereira
D048948:14-3-3 Proteins / Q000502:physiology; D015825:Chromosomes, Fungal / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D059566:M Phase Cell Cycle Checkpoints; D010766:Phosphorylation; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D021381:Protein Transport; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism* / Q000502:physiology*; D008941:Spindle Apparatus / Q000378:metabolism
D048948:14-3-3 Proteins; C119117:BFA1 protein, S cerevisiae; C075852:BMH1 protein, S cerevisiae; D003598:Cytoskeletal Proteins; D029701:Saccharomyces cerevisiae Proteins; C503719:KIN4 kinase, S cerevisiae; D017346:Protein Serine-Threonine Kinases