Interactions Between the Kinetochore Complex and the Protein Kinase A Pathway in Saccharomyces cerevisiae

G3: Genes, Genomes, Genetics

Krystina Ho³  Zongli Luo²  Lina Ma¹  Vivien Measday²  Nina Piggott² 

[1] Wine Research Centre, Faculty of Land and Food SystemsGenetics Graduate ProgramWine Research Centre, Faculty of Land and Food SystemsWine Research Centre, Faculty of Land and Food SystemsGenetics Graduate ProgramGenetics Graduate ProgramWine Research Centre, Faculty of Land and Food SystemsGenetics Graduate Program;Wine Research Centre, Faculty of Land and Food SystemsWine Research Centre, Faculty of Land and Food SystemsWine Research Centre, Faculty of Land and Food Systems;Wine Research Centre, Faculty of Land and Food SystemsGraduate Program in Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, CWine Research Centre, Faculty of Land and Food SystemsWine Research Centre, Faculty of Land and Food SystemsGraduate Program in Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, CGraduate Program in Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, CWine Research Centre, Faculty of Land and Food SystemsGraduate Program in Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z4, C

关键词: budding yeast;    protein kinase A;    kinetochore;    chromosome segregation;    spindle checkpoint;   

DOI  :  10.1534/g3.112.002675

学科分类：生物科学（综合）

来源: Genetics Society of America

【 摘 要 】

The kinetochore is a large structure composed of multiple protein subcomplexes that connect chromosomes to spindle microtubules to enable accurate chromosome segregation. Significant advances have been made in the identification of kinetochore proteins and elucidation of kinetochore structure; however, comparatively little is known about how cellular signals integrate with kinetochore function. In the budding yeast Saccharomyces cerevisiae, the cyclic AMP protein kinase A signaling pathway promotes cellular growth in response to glucose. In this study, we find that decreasing protein kinase A activity, either by overexpressing negative regulators of the pathway or deleting the upstream effector Ras2, improves the viability of ipl1 and spc24 kinetochore mutants. Ipl1/Aurora B is a highly conserved kinase that corrects attachment of sister kinetochores that have attached to the same spindle pole, whereas Spc24 is a component of the conserved Ndc80 kinetochore complex that attaches directly to microtubules. Unexpectedly, we find that kinetochore mutants have increased phosphorylation levels of protein kinase A substrates, suggesting that the cyclic AMP protein kinase A signaling pathway is stimulated. The increase in protein kinase A activity in kinetochore mutants is not induced by activation of the spindle checkpoint or a metaphase delay because protein kinase A activity remains constant during an unperturbed cell cycle. Finally, we show that lowering protein kinase A activity can rescue the chromosome loss defect of the inner kinetochore ndc10 mutant. Overall, our data suggest that the increased protein kinase A activity in kinetochore mutants is detrimental to cellular growth and chromosome transmission fidelity.

【 授权许可】

Unknown