Cell. 2024 Mar 6;187(6). doi: 10.1016/j.cell.2024.02.014.
Proteome-scale movements and compartment-connectivity during the eukaryotic cell cycle

Athanasios Litsios1,8, Benjamin T. Grys1,2,8, Oren Z. Kraus1,3,8, Helena Friesen1, Catherine Ross1, Myra Paz David Masinas1, Duncan Forster1,2, Mary T. Couvillion4, Stefanie Timmermann5, Maximilian Billmann6, Chad Myers6, Nils Johnsson5, L. Stirling Churchman4, Charles Boone1,2,7,*, and Brenda J. Andrews1,2,Ŧ

  • 1Donnelly Centre for Cellular and Biomolecular Research, University of Toronto, Toronto, ON, M5S 3E1, Canada
  • 2Department of Molecular Genetics, University of Toronto, Toronto, ON, M5S 1A8, Canada
  • 3Department of Electrical and Computer Engineering, University of Toronto, Toronto, ON, M5S 3G4, Canada
  • 4Department of Genetics, Harvard Medical School, Boston, MA, 02115, USA
  • 5Institute of Molecular Genetics and Cell Biology, Department of Biology, Ulm University, Ulm, D-89081, Germany
  • 6Department of Computer Science and Engineering, University of Minnesota, Minneapolis, MN, 55455, USA
  • 7RIKEN Center for Sustainable Resource Science, Wako, 351-0198 Saitama, Japan

  • 8 These authors contributed equally to this work
  • * Corresponding authors
  • Ŧ Lead contact

  • * Correspondence: brenda.andrews@utoronto.ca, charlie.boone@utoronto.ca

Abstract

Cell cycle progression relies on coordinated changes in the composition and subcellular localization of the proteome. By applying two distinct convolutional neural networks on images of millions of live yeast cells, we resolved proteome-level dynamics in both concentration and localization during the cell cycle, with resolution of ~20 subcellular localization classes. We show that a quarter of the proteome displays cell cycle periodicity, with proteins tending to be controlled either at the level of localization or concentration, but not both. Distinct levels of protein regulation are preferentially utilized for different aspects of the cell cycle, with changes in protein concentration being mostly involved in cell cycle control, while changes in protein localization in the biophysical implementation of the cell cycle program. We present a resource for exploring global proteome dynamics during the cell cycle, which will aid in understanding a fundamental biological process at a systems level.