title: Binding of Drosophila Polo kinase to its regulator Matrimony is noncanonical and involves two separate functional domains.
abstract: 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.
authors.affiliation: Stowers Institute for Medical Research, Kansas City, MO 64110, USA.
authors.forename: Amanda M
authors.initials: AM
authors.lastname: Bonner
authors.forename: Stacie E
authors.initials: SE
authors.lastname: Hughes
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Chisholm
authors.forename: S Kendall
authors.initials: SK
authors.lastname: Smith
authors.forename: Brian D
authors.initials: BD
authors.lastname: Slaughter
authors.forename: Jay R
authors.initials: JR
authors.lastname: Unruh
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Collins
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Friederichs
authors.forename: Laurence
authors.initials: L
authors.lastname: Florens
authors.forename: Selene K
authors.initials: SK
authors.lastname: Swanson
authors.forename: Marissa C
authors.initials: MC
authors.lastname: Pelot
authors.forename: Danny E
authors.initials: DE
authors.lastname: Miller
authors.forename: Michael P
authors.initials: MP
authors.lastname: Washburn
authors.forename: Sue L
authors.initials: SL
authors.lastname: Jaspersen
authors.forename: R Scott
authors.initials: RS
authors.lastname: Hawley
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster; D005260:Female; D008297:Male; D008540:Meiosis / Q000502:physiology*; D010766:Phosphorylation / Q000502:physiology; D011485:Protein Binding / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D013050:Spectrometry, Fluorescence
chemical_list: D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; C531345:mtrm protein, Drosophila; C072004:polo protein, Drosophila; D017346:Protein Serine-Threonine Kinases