Spindle Position Checkpoint Kinase Kin4 Regulates Organelle Transport in Saccharomyces cerevisiae

Biomolecules. 2023 Jul 10;13(7):1098. doi: 10.3390/biom13071098.

Abstract

Membrane-bound organelles play important, frequently essential, roles in cellular metabolism in eukaryotes. Hence, cells have evolved molecular mechanisms to closely monitor organelle dynamics and maintenance. The actin cytoskeleton plays a vital role in organelle transport and positioning across all eukaryotes. Studies in the budding yeast Saccharomyces cerevisiae (S. cerevisiae) revealed that a block in actomyosin-dependent transport affects organelle inheritance to daughter cells. Indeed, class V Myosins, Myo2, and Myo4, and many of their organelle receptors, have been identified as key factors in organelle inheritance. However, the spatiotemporal regulation of yeast organelle transport remains poorly understood. Using peroxisome inheritance as a proxy to study actomyosin-based organelle transport, we performed an automated genome-wide genetic screen in S. cerevisiae. We report that the spindle position checkpoint (SPOC) kinase Kin4 and, to a lesser extent, its paralog Frk1, regulates peroxisome transport, independent of their role in the SPOC. We show that Kin4 requires its kinase activity to function and that both Kin4 and Frk1 protect Inp2, the peroxisomal Myo2 receptor, from degradation in mother cells. In addition, vacuole inheritance is also affected in kin4/frk1-deficient cells, suggesting a common regulatory mechanism for actin-based transport for these two organelles in yeast. More broadly our findings have implications for understanding actomyosin-based transport in cells.

Keywords: actin cytoskeleton; class V myosin; mitotic exit network (MEN); organelle transport; peroxisome; spindle position checkpoint (SPOC).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Actomyosin / metabolism
  • Mitosis
  • Organelles
  • Protein Kinases / metabolism
  • Protein Serine-Threonine Kinases / metabolism
  • Saccharomyces cerevisiae Proteins* / genetics
  • Saccharomyces cerevisiae Proteins* / metabolism
  • Saccharomyces cerevisiae* / genetics
  • Saccharomyces cerevisiae* / metabolism
  • Spindle Apparatus / metabolism

Substances

  • Protein Serine-Threonine Kinases
  • Protein Kinases
  • Saccharomyces cerevisiae Proteins
  • Actomyosin

Grants and funding

This research was supported by the Vice Chancellor’s Indian Scholarship awarded to L.E. by The University of Sheffield, United Kingdom (App. 149647784) and a PhD scholarship awarded to Abdulaziz MS Alqahtani by The Royal Embassy of Saudi Arabia Cultural Bureau in London and the University of Bisha Saudi Arabia. Collaborative work between the MS and EH lab is supported through a WIS-UK “Making Connections” joint research programme grant. MS is an incumbent of the Dr Gilbert Omenn and Martha Darling Chair in Molecular Genetics. The robotic setup of the Schuldiner lab was supported through the generous donation of the Blythe Brenden-Mann Foundation.