title: Linking cell division to cell growth in a spatiotemporal model of the cell cycle.
abstract: Cell division must be tightly coupled to cell growth in order to maintain cell size, yet the mechanisms linking these two processes are unclear. It is known that almost all proteins involved in cell division shuttle between cytoplasm and nucleus during the cell cycle; however, the implications of this process for cell cycle dynamics and its coupling to cell growth remains to be elucidated. We developed mathematical models of the cell cycle which incorporate protein translocation between cytoplasm and nucleus. We show that protein translocation between cytoplasm and nucleus not only modulates temporal cell cycle dynamics, but also provides a natural mechanism coupling cell division to cell growth. This coupling is mediated by the effect of cytoplasmic-to-nuclear size ratio on the activation threshold of critical cell cycle proteins, leading to the size-sensing checkpoint (sizer) and the size-independent clock (timer) observed in many cell cycle experiments.
authors.affiliation: Department of Medicine (Cardiology), Cardiovascular Research Laboratory, University of California, David Geffen School of Medicine at UCLA, 47-123 CHS, 10833 Le Conte Ave., Los Angeles, CA 90095, USA.
authors.forename: Ling
authors.initials: L
authors.lastname: Yang
authors.forename: Zhangang
authors.initials: Z
authors.lastname: Han
authors.forename: W
authors.initials: W
authors.lastname: Robb MacLellan
authors.forename: James N
authors.initials: JN
authors.lastname: Weiss
authors.forename: Zhilin
authors.initials: Z
authors.lastname: Qu
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D002467:Cell Nucleus / Q000378:metabolism*; D048429:Cell Size; D003593:Cytoplasm / Q000378:metabolism*; D008954:Models, Biological; D021381:Protein Transport; D013997:Time Factors
chemical_list: D018797:Cell Cycle Proteins