Abstract
The precise coordination of growth and proliferation has a universal prevalence in cell homeostasis. As a prominent property, cell size is modulated by the coordination between these processes in bacterial, yeast, and mammalian cells, but the underlying molecular mechanisms are largely unknown. Here, we show that multifunctional chaperone systems play a concerted and limiting role in cell-cycle entry, specifically driving nuclear accumulation of the G1 Cdk-cyclin complex. Based on these findings, we establish and test a molecular competition model that recapitulates cell-cycle-entry dependence on growth rate. As key predictions at a single-cell level, we show that availability of the Ydj1 chaperone and nuclear accumulation of the G1 cyclin Cln3 are inversely dependent on growth rate and readily respond to changes in protein synthesis and stress conditions that alter protein folding requirements. Thus, chaperone workload would subordinate Start to the biosynthetic machinery and dynamically adjust proliferation to the growth potential of the cell.
Highlights
Under unperturbed conditions, growth cells maintain their size within constant limits, and different pathways have concerted roles in processes leading to growth and proliferation (Cook & Tyers, 2007; Marshall et al, 2012; Turner et al, 2012)
As key predictions of the model, we show that nuclear accumulation of the G1 cyclin Cln3 is negatively affected by growth rate in a chaperone-dependent manner and rapidly responds to conditions that perturb or boost chaperone activity
Cln3 contains a bipartite nuclear localization signal at its C terminus that is essential for timely entry into the cell cycle (Edgington & Futcher, 2001; Miller & Cross, 2001), and we had found that the Ydj1 chaperone is important for nuclear accumulation of Cln3 (Verges et al, 2007) and for setting the critical size as a function of growth rate (Ferrezuelo et al, 2012)
Summary
Growth cells maintain their size within constant limits, and different pathways have concerted roles in processes leading to growth and proliferation (Cook & Tyers, 2007; Marshall et al, 2012; Turner et al, 2012). Cell growth is dictated by many environmental factors in budding yeast, and the rate at which cells grow has profound effects on their size. High rates of macromolecular synthesis promote growth and increase cell size. Conditions that reduce cell growth limit macromolecular synthesis and reduce cell size. This behavior is nearly universal, and it has been well characterized in bacteria, yeast, diatoms, and mammalian cells of different origins (Aldea et al, 2017). A current view sustains that cell cycle and cell growth machineries should be deeply interconnected to ensure cell homeostasis and adaptation, but the causal molecular mechanism is still poorly understood (Lloyd, 2013)
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
