Signal processing through a generalized module of adaptation and spatial sensing

2012

BMC Systems Biology

BackgroundSpatial signal transduction plays a vital role in many intracellular processes such as eukaryotic chemotaxis, polarity generation and cell division. Furthermore it is being increasingly realized that the spatial dimension to signalling may play an important role in other apparently purely temporal signal transduction processes. It is increasingly being recognized that a conceptual basis for studying spatial signal transduction in signalling networks is necessary.ResultsIn this work we examine spatial signal transduction in a series of standard motifs/networks. These networks include coherent and incoherent feedforward, positive and negative feedback, cyclic motifs, monostable switches, bistable switches and negative feedback oscillators. In all these cases, the driving signal has spatial variation. For each network we consider two cases, one where all elements are essentially non-diffusible, and the other where one of the network elements may be highly diffusible. A careful analysis of steady state signal transduction provides many insights into the behaviour of all these modules. While in the non-diffusible case for the most part, spatial signalling reflects the temporal signalling behaviour, in the diffusible cases, we see significant differences between spatial and temporal signalling characteristics. Our results demonstrate that the presence of diffusible elements in the networks provides important constraints and capabilities for signalling.ConclusionsOur results provide a systematic basis for understanding spatial signalling in networks and the role of diffusible elements therein. This provides many insights into the signal transduction capabilities and constraints in such networks and suggests ways in which cellular signalling and information processing is organized to conform to or bypass those constraints. It also provides a framework for starting to understand the organization and regulation of spatial signal transduction in individual processes.

Section: Methodsmentioning

confidence: 99%

An investigation of spatial signal transduction in cellular networks

Alam-Nazki¹,

2012

BMC Systems Biology

“…In our modelling of the adaptive regulation of PI3K by the receptor signal, we describe the regulation of PI3K localization via a strongly diffusing activator enzyme (A) and a locally acting inhibitor enzyme (I) (Krishnan, 2009). These enzymes are regulated in a non linear fashion by the receptor signal as in Ma, et al (2004) (very similar results are seen if this regulation is linear (Alam-Nazki, 2008)).…”

Section: Pi3k-pip 2 -Pip 3 Pathwaymentioning

confidence: 98%

“…However, in this case the activator acts locally and the inhibitor is capable of long range diffusion (Ma et al, 2004;Krishnan, 2009). The final equations of the model where k -ten and k ten are the reaction rate constants for the conversion between PTEN mem and PTEN cy .…”

Section: Accepted Manuscript 12mentioning

confidence: 99%

A mathematical modelling framework for understanding chemorepulsive signal transduction in Dictyostelium

Alam-Nazki

Journal of Theoretical Biology

2010

Self Cite

Chemorepulsion is the process by which an organism or a cell moves in the direction of decreasing chemical concentration. While a few experimental studies have been performed, no mathematical models exist for this process. In this paper we have modelled gradient sensing, the first subprocess of chemorepulsion, in D. discoideum-a well characterized model eukaryotic system. We take the first steps towards achieving a comprehensive mechanistic understanding of chemorepulsion in this system. We have used, as a basis, the biochemical network of the Keizer-Gunnink et al. (2007)

“…For our purposes we will employ a compact model which gives rise to adaptive signalling and spatial responses. Since, we will be considering both attractive and repulsive responses, we choose a generalization of the local excitation global inhibition model developed previously (Krishnan, 2009). This involves a response element R * to be regulated by an activator and inhibitor both of which may be diffusible.…”

Section: Modelsmentioning

confidence: 99%

An investigation of design principles underlying repulsive and attractive gradient sensing and their switching

Journal of Theoretical Biology

Alam-Nazki

2011

Self Cite

Cite this article as: J. Krishnan and Aiman Alam-Nazki, An investigation of design principles underlying repulsive and attractive gradient sensing and their switching, Journal of Theoretical Biology, doi:10.1016Biology, doi:10. /j.jtbi.2010 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting galley proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.