Dataset Information

Xu2003 - Phosphoinositide turnover

ABSTRACT: Xu2003 - Phosphoinositide turnover The model reproduces the percentage change of PIP_PM, PIP2_PM and IP3_Cyt as depicted in Figure 1 of the paper. The model also contains the equations for the analysis of PH-GFP experiments, however the initial value of PH_GFP has been set to zero to more accurately reproduce Figure 1. The units of cytosolic species are given in molecules/um^3. In order to convert them to uM, divide the concentration by 602. For the analysis of PH_GFP experiments, one should plug in the values of PH_GFP, IP3_PHGFP and PIP2_PHGFP from Table AI in the appendix. The model was successfully tested on MathSBML. This model has been generated by VCell This model is described in the article: Kinetic analysis of receptor-activated phosphoinositide turnover. Xu C, Watras J, Loew LM. J. Cell Biol. 2003 May; 161(4): 779-791 Abstract: We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2-3 min. However, the rate and amount of inositol-1,4,5-trisphosphate (InsP3) production were much greater than the rate or amount of PIP2 decline. A mathematical model of phosphoinositide turnover based on this data predicted that PIP2 synthesis is also stimulated by bradykinin, causing an early transient increase in its concentration. This was subsequently confirmed experimentally. Then, we used single-cell microscopy to further examine phosphoinositide turnover by following the translocation of the pleckstrin homology domain of PLCdelta1 fused to green fluorescent protein (PH-GFP). The observed time course could be simulated by incorporating binding of PIP2 and InsP3 to PH-GFP into the model that had been used to analyze the biochemistry. Furthermore, this analysis could help to resolve a controversy over whether the translocation of PH-GFP from membrane to cytosol is due to a decrease in PIP2 on the membrane or an increase in InsP3 in cytosol; by computationally clamping the concentrations of each of these compounds, the model shows how both contribute to the dynamics of probe translocation. This model is hosted on BioModels Database and identified by: BIOMD0000000075 . To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models . To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

SUBMITTER: Harish Dharuri

PROVIDER: BIOMD0000000075 | BioModels | 2019-05-16

REPOSITORIES: BioModels

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Publications

Kinetic analysis of receptor-activated phosphoinositide turnover.

Xu Chang C Watras James J Loew Leslie M LM

The Journal of cell biology 20030501 4

We studied the bradykinin-induced changes in phosphoinositide composition of N1E-115 neuroblastoma cells using a combination of biochemistry, microscope imaging, and mathematical modeling. Phosphatidylinositol-4,5-bisphosphate (PIP2) decreased over the first 30 s, and then recovered over the following 2-3 min. However, the rate and amount of inositol-1,4,5-trisphosphate (InsP3) production were much greater than the rate or amount of PIP2 decline. A mathematical model of phosphoinositide turnover ...[more]

PMID: 12771127

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Project description:Staphylococcus aureus is a leading cause of hospital- and community-associated infections. The organism’s ability to cause disease can, in part, be attributable to its ability to adapt to otherwise deleterious host-associated stresses. Like other bacterial species, the modulation of mRNA turnover appears to play an important role in S. aureus adaptation to certain environmental stresses. In the current study Affymetrix GeneChips® were used to examine the S. aureus responses to acid and alkaline shock-inducing conditions and to assess whether stress dependent changes in mRNA turnover are likely to facilitate the organism’s ability to tolerate extreme pH challenge. Results indicate that S. aureus adapts to pH shock by eliciting responses expected of organisms coping with pH alteration, including neutralizing cellular internal pH, DNA repair, amino acid biosynthesis and virulence factor expression. Further, it was found that the cellular response to alkaline conditions elicits a transcriptional profile that is similar to that of stringent response induced cells. Consistent with that observation, we show that the activator of the stringent response, (p)ppGpp, levels are profoundly elevated during alkaline shock conditions. We also show that the mRNA turnover properties of acid or alkaline shocked cells significantly differ from that of cells grown at neutral pH. A comparison of the mRNA degradation properties of transcripts whose titers either increased or decreased in response to sudden pH change revealed that alterations in mRNA degradation may, in part, account for the changes in the mRNA levels of factors predicted to mediate pH tolerance. Finally, a set of small stable RNA molecules were induced in response to acid or alkaline shock conditions. As in other organisms, these molecules may mediate mRNA stability and adaptation to otherwise deleterious growth conditions. Staphylococcus aureus strain UAMS-1 was grown to exponential phase and either mock treated (pH maintained at 7.4) or subjected to acid (pH 4)- or alkaline (pH 10) conditions for 30 min. Next, 200 micrograms per ml of rifampicin were added to arrest transcript synthesis. RNA was extracted from cell suspensions at 0, 2.5, 5, 15, and 30 min post-transcriptional arrest, labeled and hybridized to S. aureus GeneChips. A comparison of 0 min samples allowed assessment of acid and alkaline shock responses. A comparison of 0 min to that of various post-transcriptional arrest RNA samples allowed assessment of the mRNA turnover properties of mock vs acid or alkaline shocked cells. Duplicates of each experimental condition and corresponding post-transcriptional arrest time point were used (biological replicates).

Dataset Information

Xu2003 - Phosphoinositide turnover

Publications

Kinetic analysis of receptor-activated phosphoinositide turnover.

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