Bonner, A.M., Hughes, S.E., Chisholm, J.A., Smith, S.K., Slaughter, B.D., Unruh, J.R., Collins, K.A., Friederichs, J.M., Florens, L., Swanson, S.K., Pelot, M.C., Miller, D.E., Washburn, M.P., Jaspersen, S.L., Hawley, R.S. (2013). Binding of Drosophila Polo kinase to its regulator Matrimony is noncanonical and involves two separate functional domains.  Proc. Natl. Acad. Sci. U.S.A. 110(13): E1222--E1231.

FBrf0221228

Research paper

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 design of a new class of Polo inhibitors to be used as targeted anticancer therapeutic agents.

PMC3612667 (PMC) (EuropePMC)