Cell Shape and Negative Links in Regulatory Motifs Together Control Spatial Information Flow in Signaling Networks

Susana R. Neves; Panayiotis Tsokas; Anamika Sarkar; Elizabeth A. Grace; Padmini Rangamani; Stephen M. Taubenfeld; Cristina M. Alberini; James C. Schaff; Robert D. Blitzer; Ion I. Moraru; Ravi Iyengar

doi:10.1016/j.cell.2008.04.025

Cell Shape and Negative Links in Regulatory Motifs Together Control Spatial Information Flow in Signaling Networks

Susana R. Neves, Panayiotis Tsokas, Anamika Sarkar, Elizabeth A. Grace, Padmini Rangamani, Stephen M. Taubenfeld, Cristina M. Alberini, James C. Schaff, Robert D. Blitzer, Ion I. Moraru, Ravi Iyengar

Neural Science

Research output: Contribution to journal › Article › peer-review

Abstract

The role of cell size and shape in controlling local intracellular signaling reactions, and how this spatial information originates and is propagated, is not well understood. We have used partial differential equations to model the flow of spatial information from the β-adrenergic receptor to MAPK1,2 through the cAMP/PKA/B-Raf/MAPK1,2 network in neurons using real geometries. The numerical simulations indicated that cell shape controls the dynamics of local biochemical activity of signal-modulated negative regulators, such as phosphodiesterases and protein phosphatases within regulatory loops to determine the size of microdomains of activated signaling components. The model prediction that negative regulators control the flow of spatial information to downstream components was verified experimentally in rat hippocampal slices. These results suggest a mechanism by which cellular geometry, the presence of regulatory loops with negative regulators, and key reaction rates all together control spatial information transfer and microdomain characteristics within cells.

Original language	English (US)
Pages (from-to)	666-680
Number of pages	15
Journal	Cell
Volume	133
Issue number	4
DOIs	https://doi.org/10.1016/j.cell.2008.04.025
State	Published - May 16 2008

Keywords

MOLNEURO
SIGNALING
SYSBIO

ASJC Scopus subject areas

General Biochemistry, Genetics and Molecular Biology

Access to Document

10.1016/j.cell.2008.04.025

Cite this

@article{f2527cab9bfe40fe8d6693ac970cb46a,

title = "Cell Shape and Negative Links in Regulatory Motifs Together Control Spatial Information Flow in Signaling Networks",

abstract = "The role of cell size and shape in controlling local intracellular signaling reactions, and how this spatial information originates and is propagated, is not well understood. We have used partial differential equations to model the flow of spatial information from the β-adrenergic receptor to MAPK1,2 through the cAMP/PKA/B-Raf/MAPK1,2 network in neurons using real geometries. The numerical simulations indicated that cell shape controls the dynamics of local biochemical activity of signal-modulated negative regulators, such as phosphodiesterases and protein phosphatases within regulatory loops to determine the size of microdomains of activated signaling components. The model prediction that negative regulators control the flow of spatial information to downstream components was verified experimentally in rat hippocampal slices. These results suggest a mechanism by which cellular geometry, the presence of regulatory loops with negative regulators, and key reaction rates all together control spatial information transfer and microdomain characteristics within cells.",

keywords = "MOLNEURO, SIGNALING, SYSBIO",

author = "Neves, {Susana R.} and Panayiotis Tsokas and Anamika Sarkar and Grace, {Elizabeth A.} and Padmini Rangamani and Taubenfeld, {Stephen M.} and Alberini, {Cristina M.} and Schaff, {James C.} and Blitzer, {Robert D.} and Moraru, {Ion I.} and Ravi Iyengar",

note = "Funding Information: This research was supported by NIH grants GM072853 and DK 38761. S.R.N. was supported by NRSA GM-65065. Additional support was provided by the NIH Nanomedicine Center (PN2EY016586) and the System Biology Center (PSDGM071558). We thank Dr. M Loshe for the cAMP FRET probe; Drs. G Huntley, D. Benson, and V. Nagy for helpful advice regarding immunohistochemistry experiments: Dr. A. Lipshtat for critical comments on curve fitting; and Dr. S. Shvartsman (Princeton University) for helpful comments. We thank Dr. R. Tsien for valuable questions during an oral presentation by one of us (R.I.) that led to the design of the simulations in Figure 6 . ",

year = "2008",

month = may,

day = "16",

doi = "10.1016/j.cell.2008.04.025",

language = "English (US)",

volume = "133",

pages = "666--680",

journal = "Cell",

issn = "0092-8674",

publisher = "Elsevier B.V.",

number = "4",

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T1 - Cell Shape and Negative Links in Regulatory Motifs Together Control Spatial Information Flow in Signaling Networks

AU - Neves, Susana R.

AU - Tsokas, Panayiotis

AU - Sarkar, Anamika

AU - Grace, Elizabeth A.

AU - Rangamani, Padmini

AU - Taubenfeld, Stephen M.

AU - Alberini, Cristina M.

AU - Schaff, James C.

AU - Blitzer, Robert D.

AU - Moraru, Ion I.

AU - Iyengar, Ravi

N1 - Funding Information: This research was supported by NIH grants GM072853 and DK 38761. S.R.N. was supported by NRSA GM-65065. Additional support was provided by the NIH Nanomedicine Center (PN2EY016586) and the System Biology Center (PSDGM071558). We thank Dr. M Loshe for the cAMP FRET probe; Drs. G Huntley, D. Benson, and V. Nagy for helpful advice regarding immunohistochemistry experiments: Dr. A. Lipshtat for critical comments on curve fitting; and Dr. S. Shvartsman (Princeton University) for helpful comments. We thank Dr. R. Tsien for valuable questions during an oral presentation by one of us (R.I.) that led to the design of the simulations in Figure 6 .

PY - 2008/5/16

Y1 - 2008/5/16

N2 - The role of cell size and shape in controlling local intracellular signaling reactions, and how this spatial information originates and is propagated, is not well understood. We have used partial differential equations to model the flow of spatial information from the β-adrenergic receptor to MAPK1,2 through the cAMP/PKA/B-Raf/MAPK1,2 network in neurons using real geometries. The numerical simulations indicated that cell shape controls the dynamics of local biochemical activity of signal-modulated negative regulators, such as phosphodiesterases and protein phosphatases within regulatory loops to determine the size of microdomains of activated signaling components. The model prediction that negative regulators control the flow of spatial information to downstream components was verified experimentally in rat hippocampal slices. These results suggest a mechanism by which cellular geometry, the presence of regulatory loops with negative regulators, and key reaction rates all together control spatial information transfer and microdomain characteristics within cells.

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JO - Cell

JF - Cell

IS - 4

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Cell Shape and Negative Links in Regulatory Motifs Together Control Spatial Information Flow in Signaling Networks

Abstract

Keywords

ASJC Scopus subject areas

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