The kinase domain of CK1 enzymes contains the localization cue essential for compartmentalized signaling at the spindle pole

Mol Biol Cell. 2018 Jul 1;29(13):1664-1674. doi: 10.1091/mbc.E18-02-0129. Epub 2018 May 9.

Abstract

CK1 protein kinases contribute to multiple biological processes, but how they are tailored to function in compartmentalized signaling events is largely unknown. Hhp1 and Hhp2 (Hhp1/2) are the soluble CK1 family members in Schizosaccharomyces pombe. One of their functions is to inhibit the septation initiation network (SIN) during a mitotic checkpoint arrest. The SIN is assembled by Sid4 at spindle pole bodies (SPBs), and though Hhp1/2 colocalize there, it is not known how they are targeted there or whether their SPB localization is required for SIN inhibition. Here, we establish that Hhp1/2 localize throughout the cell cycle to SPBs, as well as to the nucleus, cell tips, and division site. We find that their catalytic domains but not their enzymatic function are used for SPB targeting and that this targeting strategy is conserved in human CK1δ/ε localization to centrosomes. Further, we pinpoint amino acids in the Hhp1 catalytic domain required for SPB interaction; mutation of these residues disrupts Hhp1 association with the core SPB protein Ppc89, and the inhibition of cytokinesis in the setting of spindle stress. Taken together, these data have enabled us to define a molecular mechanism used by CK1 enzymes to target a specific cellular locale for compartmentalized signaling.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Biocatalysis
  • Catalytic Domain
  • Cell Compartmentation*
  • Cell Cycle
  • Centrosome / metabolism
  • Models, Molecular
  • Protein Kinases / chemistry*
  • Protein Kinases / metabolism*
  • Protein Transport
  • Schizosaccharomyces / enzymology
  • Schizosaccharomyces pombe Proteins / chemistry*
  • Schizosaccharomyces pombe Proteins / metabolism*
  • Signal Transduction*
  • Spindle Pole Bodies / metabolism
  • Spindle Poles / metabolism*
  • Structure-Activity Relationship

Substances

  • Schizosaccharomyces pombe Proteins
  • Protein Kinases
  • hhp1 protein, S pombe
  • hhp2 protein, S pombe