Enzymatically Driven Transport: A Kinetic Theory for Nuclear Export

Kim, Sanghyun; Elbaum, Michael

doi:10.1016/j.bpj.2013.09.011

Cited by 12 publications

(18 citation statements)

References 21 publications

(26 reference statements)

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“…The final steady state accumulation and the late kinetics of the capsid import are affected by a number of factors that are still incompletely understood – such as the competition between Ran and NTRs for the cargo, the back leakage of the cargo into the cytoplasm and potential clogging of the pores by the capsids ( Kim and Elbaum, 2013a ; Kim and Elbaum, 2013b ). For this reason, we focus our quantitative analysis on the initial flux J (slope of the kinetic curve at the initial time point).…”

Section: Resultsmentioning

confidence: 99%

Molecular determinants of large cargo transport into the nucleus

Paci

Zheng

Caria

et al. 2020

eLife

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Nucleocytoplasmic transport is tightly regulated by the nuclear pore complex (NPC). Among the thousands of molecules that cross the NPC, even very large (>15 nm) cargoes such as pathogens, mRNAs and pre-ribosomes can pass the NPC intact. For these cargoes, there is little quantitative understanding of the requirements for their nuclear import, especially the role of multivalent binding to transport receptors via nuclear localisation sequences (NLSs) and the effect of size on import efficiency. Here, we assayed nuclear import kinetics of 30 large cargo models based on four capsid-like particles in the size range of 17–36 nm, with tuneable numbers of up to 240 NLSs. We show that the requirements for nuclear transport can be recapitulated by a simple two-parameter biophysical model that correlates the import flux with the energetics of large cargo transport through the NPC. Together, our results reveal key molecular determinants of large cargo import in cells.

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Section: Resultsmentioning

confidence: 99%

Molecular determinants of large cargo transport into the nucleus

Paci

Zheng

Caria

et al. 2020

eLife

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“…From the expression for the dimensional flux J u in Eq. 6 and the analogous expression for J v , we get the four equations J 0 u ¼ 0; (28)…”

Section: Appendix B: Steady-state Distribution Of Tether Bindingmentioning

confidence: 99%

“…1 a summarizes the nuclear import process. Interesting kinetic models based on these steps have been developed (27)(28)(29), which treat the nuclear pore as an enzyme facilitating the Ran-driven transition of molecules between cytoplasmic and nuclear states.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Nucleocytoplasmic Transport due to Competition for Elastic Binding Sites

Fogelson

Keener

2018

Biophysical Journal

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Nuclear pore complexes (NPCs) control all traffic into and out of the cell nucleus. NPCs are molecular machines that simultaneously achieve high selectivity and high transport rates. The biophysical details of how cargoes rapidly traverse the pore remain unclear but are known to be mediated by interactions between cargo-binding chaperone proteins and natively unstructured nucleoporin proteins containing many phenylalanine-glycine repeats (FG nups) that line the pore's central channel. Here, we propose a specific and detailed physical mechanism for the high speed of nuclear import based on the elasticity of FG nups and on competition between individual chaperone proteins for FG nup binding. We develop a mathematical model to support our proposed mechanism. We suggest that the recycling of nuclear import factors back to the cytoplasm is important for driving high-speed import and predict the existence of an optimal cytoplasmic concentration of cargo for enhancing the rate of import over a purely diffusive rate.

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“…We suggest that this may limit the capacity of the nucleus to concentrate histones. The process of nuclear transport has been investigated in great detail (Kim and Elbaum, 2013a;2013b;Kopito and Elbaum, 2007; 2009) and we can assume that the nuclear envelope can create a certain fold difference in concentrations between the nucleus and cytoplasm. During the initial stages of zebrafish development, the nucleus occupies only a very small fraction of the cell volume (1.1% at 128-cell stage, Figure 4-figure supplement 1A).…”

Section: Changes In Nuclear Histone Concentration During Genome Activmentioning

confidence: 99%

Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

Joseph

Pálfy

Hilbert

et al. 2017

Preprint

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Upon fertilization, the genome of animal embryos remains transcriptionally inactive until the maternal-to-zygotic transition. At this time, the embryo takes control of its development and transcription begins. How the onset of zygotic transcription is regulated remains unclear. Here, we show that a dynamic competition for DNA binding between nucleosome-forming histones and transcription factors regulates zebrafish genome activation. Taking a quantitative approach, we found that the concentration of non-DNA-bound core histones sets the time for the onset of transcription. The reduction in nuclear histone concentration that coincides with genome activation does not affect nucleosome density on DNA, but allows transcription factors to compete successfully for DNA binding. In agreement with this, transcription factor binding is sensitive to histone levels and the concentration of transcription factors also affects the time of transcription. Our results demonstrate that the relative levels of histones and transcription factors regulate the onset of transcription in the embryo.

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Enzymatically Driven Transport: A Kinetic Theory for Nuclear Export

Cited by 12 publications

References 21 publications

Molecular determinants of large cargo transport into the nucleus

Molecular determinants of large cargo transport into the nucleus

Enhanced Nucleocytoplasmic Transport due to Competition for Elastic Binding Sites

Competition between histone and transcription factor binding regulates the onset of transcription in zebrafish embryos

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