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Signalling scaffolds and local organization of cellular behaviour.

ABSTRACT: Cellular responses to environmental cues involve the mobilization of GTPases, protein kinases and phosphoprotein phosphatases. The spatial organization of these signalling enzymes by scaffold proteins helps to guide the flow of molecular information. Allosteric modulation of scaffolded enzymes can alter their catalytic activity or sensitivity to second messengers in a manner that augments, insulates or terminates local cellular events. This Review examines the features of scaffold proteins and highlights examples of locally organized groups of signalling enzymes that drive essential physiological processes, including hormone action, heart rate, cell division, organelle movement and synaptic transmission.

SUBMITTER: Langeberg LK

PROVIDER: S-EPMC4722875 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Signalling scaffolds and local organization of cellular behaviour.

Langeberg Lorene K LK Scott John D JD

Nature reviews. Molecular cell biology 20150318 4

Cellular responses to environmental cues involve the mobilization of GTPases, protein kinases and phosphoprotein phosphatases. The spatial organization of these signalling enzymes by scaffold proteins helps to guide the flow of molecular information. Allosteric modulation of scaffolded enzymes can alter their catalytic activity or sensitivity to second messengers in a manner that augments, insulates or terminates local cellular events. This Review examines the features of scaffold proteins and h ...[more]

PMID: 25785716

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Project description:Biochemical pathways and networks are central to cellular information processing. While a broad range of studies have dissected multiple aspects of information processing in biochemical pathways, the effect of spatial organization remains much less understood. It is clear that space is central to intracellular organization, plays important roles in cellular information processing and has been exploited in evolution; additionally, it is being increasingly exploited in synthetic biology through the development of artificial compartments, in a variety of ways. In this paper, we dissect different aspects of the interplay between spatial organization and biochemical pathways, by focusing on basic building blocks of these pathways: covalent modification cycles and two-component systems, with enzymes which may be monofunctional or bifunctional. Our analysis of spatial organization is performed by examining a range of 'spatial designs': patterns of localization or non-localization of enzymes/substrates, theoretically and computationally. Using these well-characterized in silico systems, we analyse the following. (i) The effect of different types of spatial organization on the overall kinetics of modification, and the role of distinct modification mechanisms therein. (ii) How different information processing characteristics seen experimentally and studied from the viewpoint of kinetics are perturbed, or generated. (iii) How the activity of enzymes (bifunctional enzymes in particular) may be spatially manipulated, and the relationship between localization and activity. (iv) How transitions in spatial organization (encountered either through evolution or through the lifetime of cells, as seen in multiple model organisms) impacts the kinetic module (and pathway) behaviour, and how transitions in chemistry may be impacted by prior spatial organization. The basic insights which emerge are central to understanding the role of spatial organization in biochemical pathways in both bacteria and eukaryotes, and are of direct relevance to engineering spatial organization of pathways in bottom-up synthetic biology in cellular and cell-free systems.

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Signalling scaffolds and local organization of cellular behaviour.

Publications

Signalling scaffolds and local organization of cellular behaviour.

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