Mitotic partitioning of endosomes and lysosomes

Bergeland, Trygve; Widerberg, Jannicke; Bakke, Oddmund; Nordeng, Tommy W.

doi:10.1016/s0960-9822(01)00177-4

Cited by 90 publications

(91 citation statements)

References 35 publications

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“…However, spatial distributions can be uniform even in crowded environments, and even nonuniform spatial distributions can create independent partitioning statistics. Phenotypes consistent with independent segregation have indeed been reported for several cellular components despite complicated molecular mechanisms, e.g., endosomes and lysosomes (18) and symbiotic Chlorella cells (19). For macromolecules, one Escherichia coli study (20) suggested independent protein segregation, and another (6) showed that engineered mRNA transcripts follow independent or weakly disordered segregation, consistent with the observation that some transcripts clustered.…”

Section: Resultssupporting

confidence: 68%

“…2B), for example by binding to mitotic spindles or spindle poles (18,35), accurate partitioning is still hard to achieve. In cells that by chance have fewer binding sites v than organelles x, the unbound organelles will segregate randomly, and in cells with fewer organelles than binding sites, more organelles could bind to sites on one side than the other (1).…”

Section: Ordered Segregation Requires Extreme Parameters To Greatlymentioning

confidence: 99%

See 1 more Smart Citation

Random partitioning of molecules at cell division

Huh

Paulsson

2011

Proc. Natl. Acad. Sci. U.S.A.

198

240

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Many RNAs, proteins, and organelles are present in such low numbers per cell that random segregation of individual copies causes large "partitioning errors" at cell division. Even symmetrically dividing cells can then by chance produce daughters with very different composition. The size of the errors depends on the segregation mechanism: Control systems can reduce low-abundance errors, but the segregation process can also be subject to upstream sources of randomness or spatial heterogeneities that create large errors despite high abundances. Here we mathematically demonstrate how partitioning errors arise for different types of segregation mechanisms and how errors can be greatly increased by upstream heterogeneity but remarkably hard to avoid through controlled partitioning. We also show that seemingly straightforward experiments cannot be straightforwardly interpreted because very different mechanisms produce identical fits and present an approach to deal with this problem by adding binomial counting noise and testing for convexity or concavity in the partitioning error as a function of the binomial thinning parameter. The results lay a conceptual groundwork for more effective studies of heterogeneity among growing and dividing cells, whether in microbes or in differentiating tissues.A t balanced growth the abundances of cellular components are on average doubled during each cell cycle and then halved at cell division. But individual cells can deviate greatly from the average. Stochastic chemical reactions create fluctuations during the cell cycle and stochastic partitioning of components creates further fluctuations at cell division (1-4). This process perturbs concentrations and indirectly shapes molecular mechanisms by placing evolutionary constraints on reaction rates and network topologies.The variation coming from stochastic production has been closely studied in the last decade (5-13), emphasizing how it could be much greater than expected from Poisson statistics due to upstream sources of randomness (5-7), how it could be controlled (8, 9) or exploited (10, 11) depending on selective pressures, and how fluctuations can reveal properties of the underlying mechanisms (12, 13). Partitioning errors can contribute just as much to the overall heterogeneity and recent results suggest that much of the noise attributed to, e.g., gene expression may in fact originate in stochastic partitioning (14). But not even the basic guiding principles of partitioning have been identified: how partitioning errors depend on upstream spatial heterogeneity or self-control, how they affect the observable cell heterogeneity, or what they can teach us about mechanisms.The goal of this study is to provide a mathematical understanding of these principles by quantitatively modeling the heterogeneity introduced by various types of segregation mechanisms. We compare simple independent segregation where each segregating unit has a constant and independent probability of ending up in either daughter cell, to disordered segregation where...

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Section: Resultssupporting

confidence: 68%

Section: Ordered Segregation Requires Extreme Parameters To Greatlymentioning

confidence: 99%

Random partitioning of molecules at cell division

Huh

Paulsson

2011

Proc. Natl. Acad. Sci. U.S.A.

198

240

View full text Add to dashboard Cite

show abstract

“…It was shown that clustering of endosomal vehicles occurs in a directed manner, which is in favor of the second model, that involves active partitioning of the organelles over the daughter cells, most likely dependent on the mitotic spindle and interphase microtubule scaffold [40,41]. This was confirmed by the observation that soon after cytokinesis endosomal vesicles accumulate in the area of the microtubule organization center [40].…”

Section: Nuclear Envelope Reassemblymentioning

confidence: 87%

“…Bergeland et al [40] studied mitotic partitioning of early and late endosomes and observed that none of the endocytic vesicles fragmented or fused during cell division. Even though the numbers of both types of endosomes in the two daughter cells were roughly the same, no evidence for a strict mechanism guaranteeing their equal distribution was found.…”

Section: Nuclear Envelope Reassemblymentioning

confidence: 99%

Intracellular partitioning of cell organelles and extraneous nanoparticles during mitosis

Symens

Soenen

Rejman

et al. 2012

Advanced Drug Delivery Reviews

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“…C'est le cas des mitochondries dont la répartition est dépendante du réseau actine/myosine [2]. Ce serait le cas également des endosomes et des lysosomes qui seraient ségrégés équitablement entre les cellules filles du fait de leur accumulation près des pôles du fuseau mitotique [3]. Ce paradigme de la conservation de l'identité des domaines membranaires pendant la mitose, avec réparti-tion stochastique ou ordonnée de leurs éléments, a été contesté récemment par l'utilisation de nouvelles techniques d'imagerie qui permettent l'étude dynamique in vivo des différents compartiments cellulaires pendant le cycle cellulaire.…”

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