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Binding of Drosophila Polo kinase to its regulator Matrimony is noncanonical and involves two separate functional domains

作者:Amanda M. Bonner, Stacie E. Hughes, Jennifer Chisholm, S. Kendall Smith, Brian D. Slaughter, Jay R. Unruh, Kimberly A. Collins, Jennifer M Friederichs, Laurence Florens, Selene K. Swanson, Marissa C. Pelot, Danny E. Miller, Michael P. Washburn, Sue L. Jaspersen, R. Scott Hawley · 发表于:Proceedings of the National Academy of Sciences · 年份:2013 · DOI:10.1073/pnas.1301690110 · 被引用次数:31 · 研究领域:Microtubule and mitosis dynamics、14-3-3 protein interactions、Chromosomal and Genetic Variations

Drosophila melanogaster Polo kinase physically interacts with, and is repressed by, the Matrimony (Mtrm) protein during oogenesis. Females heterozygous for a deletion of the mtrm gene display defects in chromosome segregation at meiosis I. However, a complete absence of Mtrm results in both meiotic catastrophe and female sterility. We show that three phosphorylated residues in an N-terminal region in Mtrm are required for Mtrm::Polo binding. However, this binding is noncanonical; it does not require either a complete S-pS/pT-P motif in Mtrm or key residues in the Polo-box domain of Polo that allow Polo to bind phosphorylated substrates. By using fluorescence cross-correlation spectroscopy to characterize the Mtrm::Polo interaction in vivo, we show that a sterile α-motif (SAM) domain located at the C terminus of Mtrm increases the stability of Mtrm::Polo binding. Although Mtrm's C-terminal SAM domain is not required to rescue the chromosome segregation defects observed in mtrm/+ females, it is essential to prevent both meiotic catastrophe and the female sterility observed in mtrm/mtrm females. We propose that Polo's interaction with the cluster of phosphorylated residues alone is sufficient to rescue the meiosis I defect. However, the strengthening of Mtrm::Polo binding mediated by the SAM domain is necessary to prevent meiotic catastrophe and ensure female fertility. Characterization of the Mtrm::Polo interaction, as well as that of other Polo regulators, may assist in the de...