A phyletic perspective on cell growth

Abstract

Commonalities, as well as lineage-specific differences among bacteria, fungi, plants, and animals, are reviewed in the context of (1) the coordination of cell growth, (2) the flow of mass and energy affecting the physiological status of cells, (3) cytoskeletal dynamics during cell division, and (4) the coordination of cell size in multicellular organs and organisms. A comparative approach reveals that similar mechanisms are used to gauge and regulate cell size and proliferation, and shows that these mechanisms share similar modules to measure cell size, cycle status, competence, and number, as well as ploidy levels, nutrient availability, and other variables affecting cell growth. However, this approach also reveals that these modules often use nonhomologous subsystems when viewed at modular or genomic levels; that is, different lineages have evolved functionally analogous, but not genomically homologous, ways of either sensing or regulating cell size and growth, in much the same way that multicellularity has evolved in different lineages using analogous developmental modules.

Figure 1.

Schematics of the TORC1/TORC2, PI3K, and TSC1/TSC2 signaling pathways and portions of plant and yeast cell walls (CWs). (A) In conjunction with LST8 and other proteins, the TORC1/TORC2 pathway stimulates protein translation and transcription, ribosome biogenesis, messenger RNA (mRNA) stability, and actin polarization and organization. Both TORC1 and TORC2 are inhibited by the TSC1/TSC2 pathway that is, in turn, inhibited if growth factors trigger the PI3K pathway. (B) A portion of the plant plasma membrane (PM) showing two cellulose synthase terminal complexes (TCs) and three cellulose microfibrils (CMs). The TCs leave the CMs behind on the external surface of the PM as they are driven by microtubules. (C) A portion of the yeast PM and CW associated with the yeast cell wall integrity (CWI) signaling pathway that transmits mechanical stresses (in the CW and PM) through a family of Wsc1–Wsc3 and Mid1–Mid2 protein sensors to the Rho1 protein, which integrates signals from the PM membrane to govern β-glucan synthesis, actin organization, and polarized secretion.

Figure 2.

The log–log scaling relationships among cell surface area, volume, carbon content, and chlorophyll (chloro) a content, and cell-doubling rate. Regressions are reported based on model type II regression protocols. (A) The log–log relationship between surface area and volume. Dashed lines have slopes indistinguishable from those of Euclidean objects (slopes = 0.667; r² = 0.99; P < 0.0001); the solid line has a slope ≈3/4 (slope = 0.76; r² = 0.98; P < 0.0001). (B) The log–log relationship between cell carbon content (pg C per cell) and volume (and between chlorophyll a content and cell volume; see inset). The solid line has a slope <1 (slope = 0.90; r² = 0.95; P < 0.0001). (C) The log–log scaling relationship between cell DNA content and volume (and between cell DNA content and division rate; see inset). C-DNA content increases with increasing cell volume, but not at a commensurate (one-to-one) rate for heterotrophic prokaryotes and cyanobacteria (slope = 0.22; r² = 0.67; P < 0.0001), unicellular algae (slope = 0.79; r² = 0.89; P = 0.0001), or cells isolated from amphibians (slope = 0.57; r² = 0.73; P < 0.0001) or other animals. Across prokaryotes and unicellular algae, cell division rates increase to a limit with increasing DNA content (see inset). (D) The log–log relationship between cell division rate and volume. The solid line has a slope significantly <1 (slope = −0.17; r² = 0.16; P < 0.0001). (see inset for key to taxa.) Original units are in μm and pg. (Data taken from Williams 1964; Eppley and Sloan 1966; Mullin et al. 1966; Mandels et al. 1968; Taguchi 1976; Olmo 1983; Shuter et al. 1983; Langdon 1987, ; Agustí 1991; von Dassow et al. 2006, ; Connolly et al. 2008.)

Figure 3.

Schematics of models for the location of the future cell walls in E. coli, fission yeast, and land plant cells. (A) The MinCDE oscillation model for E. coli, in which the MinCDE polar zone begins assembling at one cell end, grows midcell (1), assembles at the opposing cell end (2) where it disassembles, releasing MinC, MinD, and MinE molecules, shrinks back to the cell end (3), and finally releases MinE from the E-ring (4) (adapted from Rothfield et al. 2005; Fig. 1). (B) The Pom1 gradient model for fission yeast, in which Pom1 from the cell ends diffuses toward the midcell, where it inhibits the Cdr1/Cdr2 → Wee1 → Cdr1/Cdr2 cascade that, in turn, prevents G₂/M entry (upper diagram). As the cell grows in length, the midcell Pom1 concentration drops below a critical threshold on which the Cdr1/Cdr2 → Wee1 → Cdr1/Cdr2 cascade is operative (lower diagram). (C) The microtubule (MT) force-sensing model, in which the tensile strains in the MTs tethering a nucleus in plant cells are adjusted (1), thereby positioning the nucleus at an equilibrium location where the preprophase band (2) prefigures the location and orientation of the future cell wall (3). Cells that are too large or too small have MT cytoskeletons that are unable to properly locate the nucleus (4 and 5).

Figure 4.

Comparisons of plant and animal organs differing in experimentally induced ploidy, or cell number or size, but conserving overall size. All organographically comparable diagrams are drawn to the same scale. (A–C) Median longitudinal sections through periclinal chimeras (2n, 2n, 2n = normal) of Datura shoot apices drawn to the same size (shaded areas denote nuclei; redrawn from Satina et al. 1940; Table 1). (D,E) Drosophila wings of wild type (WT) and the col¹/col¹; P[col5-cDNA]/⁺ double mutant lacking the sector area between longitudinal veins L3 and L4 (sector area denoted by shaded area; redrawn from Vervoort et al. 1999; Fig. 1A,B). (F–H) Trans-sections through pronephric tubules from 1n, 2n, and 5n Triturus viridescens larvae (shaded areas denote nuclei; redrawn from Fankhauser 1945b; Fig. 1). (I–L) Superimpositions of the outlines of Datura shoot apices (see A–C), Drosophila wings (see D–E), and pronephric tubule lumens (see F–H) differing in ploidy. (L,M) Epidermal cells of the first foliage leaves of untreated (L) and γ-radiated wheat seedlings (M; ab. mf., aborted mitotic figure) (redrawn from Foard and Haber 1961; Figs. 9 and 10). The first leaves of both seedlings are comparable in size (not shown).

Figure 5.

Schematic of a hypothetical network composed of generic modules regulating final organ size by sensing and regulating cell size and number (involving cell ploidy levels and cell-cycle status) in coordination with monitoring meristematic (stem cell) competence. Each module in the network is hypothesized to have an analog in any multicellular organism. Ancillary modules regulating cell differentiation and feedback loops are not diagramed.