QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 27 July 2004
doi: 10.1242/jcs.01294

This Article Summary Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Qu, Z. Articles by MacLellan, W. R. Search for Related Content PubMed PubMed Citation Articles by Qu, Z. Articles by MacLellan, W. R.

Coordination of cell growth and cell division: a mathematical modeling study

¹ Cardiovascular Research Laboratory, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA
² Department of Medicine (Cardiology), University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA
³ Department of Physiology, University of California, 10833 Le Conte Avenue, Los Angeles, California 90095, USA

View larger version (21K): [in a new window]   Fig. 1. Signaling pathways for cell growth. Cell growth is stimulated by insulin or insulin-like growth factors (IGF) binding to their receptors (IRS). The activated receptor recruits phosphatidylinositol 3-OH kinase [PI(3)K] to the membrane, which then phosphorylates PtdIns(4,5)P2, converting it to PtdIns(3,4,5)P3. Increased levels of PtdIns(3,4,5)P3 induce the activation of phosphoinositide-dependent protein kinase 1 (PDK1), which then stimulates 40S ribosomal protein S6 kinase (S6K). S6K mediates the phosphorylation of 40S ribosomal protein S6, which is thought to potentiate the recruitment of ribosomal-protein mRNAs from stores of messenger ribonucleoproteins (mRNps) to actively translating polysomes.

View larger version (28K): [in a new window]   Fig. 2. Cell cycle time in cdc-33 mutant fission yeast (Schizosaccharomyces pombe) cells. (A) Cycle time T versus birth length lB. Data were replotted from Fig. 4B in Sveiczer et al. (Sveiczer et al., 1996) (). Solid line: [T=105+(12.75-lB)/(0.006+0.0046lB)]. The dashed line marks the timer period T0. Inset graph shows the data for growth rate from Fig. 4E in Sveiczer et al. (Sveiczer et al., 1996) and the linear fit is: 0.006+0.0046lB (line). (B) T0 () and lC () versus number of data points fitted. (C) 2 versus number of data points fitted for nonlinear fit Eqn 11 () and for linear fit ().

View larger version (27K): [in a new window]   Fig. 3. Cell cycle time in cdc-33 wee1-6 mutant fission yeast (Schizosaccharomyces pombe) cells. (A) Cycle time T versus birth length lB. The fitting function for cycle time is: [T=95+(7.8-lB)/(0.004+0.0052lB)]. Inset graph shows the growth rate with linear fit: -0.004+0.0052lB (line). (B) T0 () and lC () as a function of the number of data points fitted. (C) 2 versus number of data points fitted for non-linear fit Eqn 11 () and for linear fit ().

View larger version (37K): [in a new window]   Fig. 4. Cycle time as a function of cell radius at mitosis (rB) for Xenopus laevis under different experimental growth conditions. Data (open circles) were taken from the indicated figures of Wang et al. (Wang et al., 2000) and the filled circles are fitted to Eqn 13 with the timer period T0, the inverse growth rate constant and the critical size rC shown on each panel. (A) Diploid wild type from Fig. 7. (B) Haploid wild type from Fig.10. (C) Diploid wild type with 100 ng/ml EGF from Fig. 13. (D-F) Progressively inhibited growth rate in diploid wild type with (D) 0.10 µg/ml cycloheximide (CHX) from Fig. 16; (E) 0.14 µg/ml CHX from Fig. 17 and (F) 0.18 µg/ml CHX from Fig. 16 in Wang et al. (Wang et al., 2000).

View larger version (19K): [in a new window]   Fig. 5. Effect of cycloheximide (CHX) on cell growth rate in Xenopus laevis. (A) The growth rate constant, 1/, versus [CHX] from the fits to the data in Fig. 4 () and the best fit to Eqn 14 (dashed line). (B) Schematic of CHX binding to and inactivating peptidyl transferase where k4 and k5 are rate constants.

View larger version (49K): [in a new window]   Fig. 6. Restriction point in HeLa cells. (A) Cell mass versus time for exponential growth (upper panel) or growth rate depending on birth size (lower panel). Shaded areas indicate 12-hour non-growing periods. The dotted horizontal lines mark the critical sizes for each growth rate. At the time of stopping cell growth, Cell 1 (green line, age 7 hours) has passed the restriction point (the critical size) but Cell 2 (red line, age 5 hours) has not. Arrows, labeled with M1, M1' etc., indicate the time of cell division. (B-D) Intermitotic time as a function of cell age for the first two mitoses and their summation. Shaded areas indicate cell age below 6 hours. Filled circles are the original data taken from Fig. 9 of Zetterberg and Larsson (Zetterberg and Larsson, 1995). Other open symbols are simulation for different growth rates: exponential growth (); constant growth rate (); and growth rate depending on birth size (). The solid lines in C are the linear fits of the data points beyond cell age 6 hours including (green line) and excluding (red line) the two points highlighted by dashed red circles. Filled circles in D are the summation of the averaged intermitotic time of M1 and M2 for each cell age excluding the four points highlighted in (B) and (C). The colored lines are the linear fits of the data points before (cyan) and after (red) cell age of 6 hours.