Mechanisms of Intracellular Scaling

Department of Molecular Biology, University of Wyoming, Laramie, Wyoming 82071
Annual Review of Cell and Developmental Biology (Impact Factor: 16.66). 07/2012; 28(1):113-35. DOI: 10.1146/annurev-cellbio-092910-154158
Source: PubMed


Cell size varies widely among different organisms as well as within the same organism in different tissue types and during development, which places variable metabolic and functional demands on organelles and internal structures. A fundamental question is how essential subcellular components scale to accommodate cell size differences. Nuclear transport has emerged as a conserved means of scaling nuclear size. A meiotic spindle scaling factor has been identified as the microtubule-severing protein katanin, which is differentially regulated by phosphorylation in two different-sized frog species. Anaphase mechanisms and levels of chromatin compaction both act to coordinate cell size with spindle and chromosome dimensions to ensure accurate genome distribution during cell division. Scaling relationships and mechanisms for many membrane-bound compartments remain largely unknown and are complicated by their heterogeneity and dynamic nature. This review summarizes cell and organelle size relationships and the experimental approaches that have elucidated mechanisms of intracellular scaling.

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    • "X. laevis is allotetraploid (a hybrid species with both parental genomes present in gametes: 36 chromosomes) and larger (10 cm adults), whereas X. tropicalis is diploid (20 chromosomes) and smaller (4 cm adults). Scaling at the organismal and genome levels is accompanied by differences in the size of the egg as well as that of subcellular structures formed in egg extracts, including nuclei and mitotic spindles (discussed below) (Levy and Heald 2012; Edens and Levy 2014b). Despite their size differences, the close phylogenetic relationship between these two species allows the production of hybrid embryos by cross-fertilization (Burki 1985; Narbonne et al. 2011). "
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    ABSTRACT: Size is a primary feature of biological systems that varies at many levels, from the organism to its constituent cells and subcellular structures. Amphibians populate some of the extremes in biological size and have provided insight into scaling mechanisms, upper and lower size limits, and their physiological significance. Body size variation is a widespread evolutionary tactic among amphibians, with miniaturization frequently correlating with direct development that occurs without a tadpole stage. The large genomes of salamanders lead to large cell sizes that necessitate developmental modification and morphological simplification. Amphibian extremes at the cellular level have provided insight into mechanisms that accommodate cell-size differences. Finally, how organelles scale to cell size between species and during development has been investigated at the molecular level, because subcellular scaling can be recapitulated using Xenopus in vitro systems. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor perspectives in biology 08/2015; DOI:10.1101/cshperspect.a019166 · 8.68 Impact Factor
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    • "ow components and processes within cells scale in size and rate with the size of the cell has become a topic of considerable interest in recent years (reviewed in Chan and Marshall 2012; Goehring and Hyman 2012; Levy and Heald 2012). For molecular machines with precise architectures (e.g., ribosomes), size is invariant , but rates of assembly and function, which depend on regulation and energy, might scale. "
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    ABSTRACT: The first 12 cleavage divisions in Xenopus embryos provide a natural experiment in size scaling, as cell radius decreases ∼16-fold with little change in biochemistry. Analyzing both natural cleavage and egg extract partitioned into droplets revealed that mitotic spindle size scales with cell size, with an upper limit in very large cells. We discuss spindle-size scaling in the small- and large-cell regimes with a focus on the "limiting-component" hypotheses. Zygotes and early blastomeres show a scaling mismatch between spindle and cell size. This problem is solved, we argue, by interphase asters that act to position the spindle and transport chromosomes to the center of daughter cells. These tasks are executed by the spindle in smaller cells. We end by discussing possible mechanisms that limit mitotic aster size and promote interphase aster growth to cell-spanning dimensions. Copyright © 2015 Cold Spring Harbor Laboratory Press; all rights reserved.
    Cold Spring Harbor perspectives in biology 08/2015; DOI:10.1101/cshperspect.a019182 · 8.68 Impact Factor
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    • "Our finding that spindles are larger after loss of Kif2a in embryos is consistent with these observations. The fact that we see larger spindles in embryos depleted of Kif2a thus supports an emerging theme that mitotic spindle size is largely controlled by regulating microtubule dynamics through microtubule depolymerases and severing proteins (Levy and Heald, 2012; Whitehead et al., 2013; Wilbur and Heald, 2013). "
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    ABSTRACT: Kif2a is a member of the kinesin-13 microtubule depolymerases that tightly regulate microtubule dynamics for many cellular processes. We characterized Kif2a depletion in Xenopus animal caps and embryos. Kif2a depletion generates defects in blastopore closure. These defects are rescued by removing the animal cap, suggesting that Kif2a depleted animal caps are not compliant enough to allow gastrulation movements. Gastrulation defects are not rescued by a Kif2a mutated in an Aurora kinase phosphorylation site suggesting that the phenotypes are caused by problems in mitosis. During animal cap mitoses, Kif2a localizes to the spindle poles and centromeres. Depletion of Kif2a generated multipolar spindles in stage 12 embryos. Kif2a depleted animal caps have anaphase lagging chromosomes in stage 9 and 10 embryos and subsequent cytokinesis failure. Later divisions have greater than two centrosomes generating extra spindle poles. Kif2a depleted embryos are also defective at coalescing extra spindle poles into a bipolar spindle. The gastrulation and mitotic phenotypes can be rescued by either human Kif2a or Kif2b, which suggests that the two homologues redundantly regulate mitosis in mammals. These studies demonstrate that defects in mitosis can inhibit large-scale developmental movements in vertebrate tissues. © 2015 by The American Society for Cell Biology.
    Molecular Biology of the Cell 01/2015; 26(5). DOI:10.1091/mbc.E13-12-0721 · 4.47 Impact Factor
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