A spatial model of cellular molecular trafficking including active transport along microtubules

Cangiani, Andrea; Natalini, Roberto

doi:10.1016/j.jtbi.2010.08.017

Cited by 48 publications

(47 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…When we added cytoskeleton inhibitors, the nuclear translocation of pSTAT5 was very slow, and it accumulated in the cytoplasm. In untreated IL-7-activated cells, pSTAT5 was found not only along microtubules, but microtubules might facilitate "fast track" nuclear import through a microtubule-importin interaction (38); the nuclear translocation of pSTAT5 might be the bottleneck in the JAK/STAT signal transduction induced by IL-7 and may require active molecular motor assistance for guidance and ushering, not for speed.…”

Section: Sted Microscopy Analysis Of Il-7-induced Membrane Microdomaimentioning

confidence: 99%

Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells

Tamarit

Bugault

Pillet

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

Background: Interleukin-7 is the master regulator of T-cell proliferation. Results: IL-7 drives its receptor in a membrane microdomain that regulates phosphorylation of associated tyrosine kinases JAK1 and JAK3, anchors IL-7 receptor to cytoskeleton and regulates STAT5 phosphorylation and nuclear translocation. Conclusion: Membrane microdomains and cytoskeleton scaffold IL-7R-signalosomes and assist signaling protein transport. Significance: Transient membrane and cytoskeleton organization shapes IL-7-signaling mechanisms in CD4 T-cells.

show abstract

Section: Sted Microscopy Analysis Of Il-7-induced Membrane Microdomaimentioning

confidence: 99%

Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells

Tamarit

Bugault

Pillet

et al. 2013

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Thus physiological delays maintained due to the semipermeability of the nuclear membrane are more typical for PDEs than for ODEs (if one does not want to deal with artificial delays represented by delay differential equations). We examined the Kedem–Katchalsky as representing passive transport mechanisms with the difference of concentrations at both sides of the membrane as the driving force for exchanges; however, bigger species are rather transported actively, which should be taken into account in more sophisticated models of nucleocytoplasmic transport [41].…”

Section: Discussionmentioning

confidence: 99%

Reaction–diffusion systems for spatio-temporal intracellular protein networks: A beginner's guide with two examples

Elias¹,

Clairambault²

2014

Computational and Structural Biotechnology Journal

View full text Add to dashboard Cite

Spatio-temporal dynamics of a variety of proteins is, among other things, regulated by post-translational modifications of these proteins. Such modifications can thus influence stability and biochemical activities of the proteins, activity and stability of their upstream targets within specific signalling pathways. Commonly used mathematical tools for such protein–protein (and/or protein-mRNA) interactions in single cells, namely, Michaelis–Menten and Hill kinetics, yielding a system of ordinary differential equations, are extended here into (non-linear) partial differential equations by taking into account a more realistic spatial representation of the environment where these reactions occur. In the modelling framework under consideration, all interactions occur in a cell divided into two compartments, the nucleus and the cytoplasm, connected by the semipermeable nuclear membrane and bounded by the impermeable cell membrane. Passive transport mechanism, modelled by the so-called Kedem–Katchalsky boundary conditions, is used here to represent migration of species throughout the nuclear membrane. Nonlinear systems of partial differential equations are solved by the semi-implicit Rothe method. Examples of two spatial oscillators are shown. Namely, these are the circadian rhythm for concentration of the FRQ protein in Neurospora crassa and oscillatory dynamics observed in the activation and regulation of the p53 protein following DNA damage in mammalian cells.

show abstract

“…In particular, extensions of the current model will consider the active transport of proteins and mRNA within the cell as mechanisms of movement in addition to diffusion (Cangiani and Natalini 2010). We also plan to model the nuclear membrane in more detail and take into account its thickness.…”

Section: Discussionmentioning

confidence: 99%

Spatio-temporal modelling of the Hes1 and p53-Mdm2 intracellular signalling pathways

Sturrock

Terry

Xirodimas

et al. 2011

Journal of Theoretical Biology

View full text Add to dashboard Cite

The correct localisation of transcription factors is vitally important for the proper functioning of many intracellular signalling pathways. Experimental data has shown that many pathways exhibit oscillations in concentrations of the substances involved, both temporally and spatially. Negative feedback loops are important components of these oscillations, providing fine regulation for the factors involved. In this paper we consider mathematical models of two such pathways -Hes1 and p53-Mdm2.Building on previous mathematical modelling approaches, we derive systems of partial differential equations to capture the evolution in space and time of the variables in the Hes1 and p53-Mdm2 systems. Through computational simulations we show that our reaction-diffusion models are able to produce sustained oscillations both spatially and temporally, accurately reflecting experimental evidence and advancing previous models. The simulations of our models also allow us to calculate a diffusion coefficient range for the variables in each mRNA and protein system, as well as ranges for other key parameters of the models, where sustained oscillations are observed. Finally, by exploiting the explicitly spatial nature of the partial differential equations, we are also able to manipulate mathematically the spatial location of the ribosomes, thus controlling where the proteins are synthesized within the cytoplasm. The results of these simulations predict an optimal distance outside the nucleus where protein synthesis should take place in order to generate sustained oscillations. Preprint submitted to Journal of Theoretical BiologyDecember 8, 2010 Using partial differential equation models, new information can be gained about the precise spatio-temporal dynamics of mRNA and proteins. The ability to determine spatial localisation of proteins within the cell is likely to yield fresh insight into a range of cellular diseases such as diabetes and cancer.

show abstract

A spatial model of cellular molecular trafficking including active transport along microtubules

Cited by 48 publications

References 55 publications

Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells

Membrane Microdomains and Cytoskeleton Organization Shape and Regulate the IL-7 Receptor Signalosome in Human CD4 T-cells

Reaction–diffusion systems for spatio-temporal intracellular protein networks: A beginner's guide with two examples

Spatio-temporal modelling of the Hes1 and p53-Mdm2 intracellular signalling pathways

Contact Info

Product

Resources

About