Mechanisms of intracellular scaling.
ABSTRACT 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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ABSTRACT: IntroductionCharacterization of the type and topography of structural changes and their alterations throughout the lifespan of individuals with autism is essential for understanding the mechanisms contributing to the autistic phenotype. The aim of this stereological study of neurons in 16 brain structures of 14 autistic and 14 control subjects from 4 to 64 years of age was to establish the course of neuronal nuclear and cytoplasmic volume changes throughout the lifespan of individuals with autism.ResultsOur data indicate that a deficit of neuronal soma volume in children with autism is associated with deficits in the volume of the neuronal nucleus and cytoplasm. The significant deficits of neuronal nuclear and cytoplasmic volumes in 13 of 16 examined subcortical structures, archicortex, cerebellum, and brainstem in 4- to 8-year-old autistic children suggest a global nature of brain developmental abnormalities, but with region-specific differences in the severity of neuronal pathology. The observed increase in nuclear volumes in 8 of 16 structures in the autistic teenagers/young adults and decrease in nuclear volumes in 14 of 16 regions in the age-matched control subjects reveal opposite trajectories throughout the lifespan. The deficit in neuronal nuclear volumes, ranging from 7% to 42% in the 16 examined regions in children with autism, and in neuronal cytoplasmic volumes from 1% to 31%, as well as the broader range of interindividual differences for the nuclear than the cytoplasmic volume deficits, suggest a partial distinction between nuclear and cytoplasmic pathology.Conclusions The most severe deficit of both neuronal nucleus and cytoplasm volume in 4-to 8-year-old autistic children appears to be a reflection of early developmental alterations that may have a major contribution to the autistic phenotype. The broad range of functions of the affected structures implies that their developmental and age-associated abnormalities contribute not only to the diagnostic features of autism but also to the broad spectrum of clinical alterations associated with autism. Lack of clinical improvement in autistic teenagers and adults indicates that the observed increase in neuron nucleus and cytoplasm volume close to control level does not normalize brain function.01/2015; 3(1):2. DOI:10.1186/s40478-015-0183-5
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ABSTRACT: How organelle size is regulated is a fundamental question in cell biology. Cell sizes vary dramatically across different species and in different tissue types, and changes in cell size are especially dramatic during early development when cell division frequently occurs in the absence of cell growth. A largely unanswered question is how the sizes of organelles and subcellular structures are regulated relative to cell size, a phenomenon we refer to as scaling. In general, organelle size and/or number are proportionately greater in larger cells to accommodate increased metabolic or specific functional requirements of the cell. These correlations are not absolute and have not been investigated for some organelles, still the phenomenon of scaling provides a useful framework for understanding organelle size control. In this chapter, we review recent studies that have utilized different Xenopus systems to illuminate physiological mechanisms of organelle size regulation. The first half of the chapter discusses the characteristics of two related Xenopus species that exhibit size differences and describes how comparisons of in vitro egg extracts from these two species have contributed to our understanding of size regulation of the nucleus and mitotic spindle. In the second half of the chapter we focus on Xenopus developmental scaling when dramatic reductions in cell size occur and highlight how this system has informed size regulation of the nucleus, spindle, and mitotic chromosomes. We conclude with a discussion of the functional implications of organelle scaling and some future prospects about how these Xenopus systems might be used to elucidate size control of other organelles and subcellular structures.Xenopus Development, Edited by Malgorzata Kloc, Jacek Z. Kubiak, 03/2014: chapter 17: pages 325-345; John Wiley & Sons, Inc.., ISBN: 978-1-118-49281-9
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ABSTRACT: Flagellar length control in Chlamydomonas reinhardtii provides a simple model system in which to investigate the general question of how cells regulate organelle size. Previous work has demonstrated that Chlamydomonas cytoplasm contains a pool of flagellar precursor proteins sufficient to assemble a half-length flagellum, and that assembly of full-length flagella requires synthesis of additional precursors to augment the pre-existing pool. The regulatory systems that control the synthesis and regeneration of this pool are not known although transcriptional regulation clearly plays a role. We used quantitative analysis of length distributions to identify candidate genes controlling pool regeneration and found that a mutation in the p80 regulatory subunit of katanin, encoded by the PF15 gene in Chlamydomonas, alters flagellar length by changing the kinetics of precursor pool utilization. This finding suggests a model in which flagella compete with cytoplasmic microtubules for a fixed pool of tubulin, with katanin-mediated severing allowing easier access to this pool during flagellar assembly. We tested this model using a stochastic simulation which confirms that cytoplasmic microtubules can compete with flagella for a limited tubulin pool, and show that alteration of cytoplasmic microtubule severing could be sufficient to explain the effect of the pf15 mutations on flagellar length.Molecular Biology of the Cell 08/2014; 25(22). DOI:10.1091/mbc.E14-06-1116 · 4.55 Impact Factor