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

Research output: Contribution to journalArticlepeer-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 languageEnglish (US)
Pages (from-to)666-680
Number of pages15
JournalCell
Volume133
Issue number4
DOIs
StatePublished - May 16 2008

Keywords

  • MOLNEURO
  • SIGNALING
  • SYSBIO

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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