The Endoplasmic Reticulum: A Central Player in Cell Signalling and Protein Synthesis

Roderick, H. Llewelyn; Berridge, Michael J.; Bootman, Martin D.

doi:10.1007/978-3-540-44878-5_2

Cited by 2 publications

(2 citation statements)

References 97 publications

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“…The ER is a tubular network spreading throughout the cell [45] . Diffusion in such a geometry can be described by diffusion in unrestricted space with a decreased diffusion coefficient [46] .…”

Section: Resultsmentioning

confidence: 99%

Calcium Signals Driven by Single Channel Noise

2010

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Usually, the occurrence of random cell behavior is appointed to small copy numbers of molecules involved in the stochastic process. Recently, we demonstrated for a variety of cell types that intracellular Ca2+ oscillations are sequences of random spikes despite the involvement of many molecules in spike generation. This randomness arises from the stochastic state transitions of individual Ca2+ release channels and does not average out due to the existence of steep concentration gradients. The system is hierarchical due to the structural levels channel - channel cluster - cell and a corresponding strength of coupling. Concentration gradients introduce microdomains which couple channels of a cluster strongly. But they couple clusters only weakly; too weak to establish deterministic behavior on cell level. Here, we present a multi-scale modelling concept for stochastic hierarchical systems. It simulates active molecules individually as Markov chains and their coupling by deterministic diffusion. Thus, we are able to follow the consequences of random single molecule state changes up to the signal on cell level. To demonstrate the potential of the method, we simulate a variety of experiments. Comparisons of simulated and experimental data of spontaneous oscillations in astrocytes emphasize the role of spatial concentration gradients in Ca2+ signalling. Analysis of extensive simulations indicates that frequency encoding described by the relation between average and standard deviation of interspike intervals is surprisingly robust. This robustness is a property of the random spiking mechanism and not a result of control.

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Section: Resultsmentioning

confidence: 99%

Calcium Signals Driven by Single Channel Noise

2010

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“…Another set of molecular targets of PI cycle activation is constituted by the protein kinase C (PKC) isozymes, which are activated by both DAG (produced by PIP 2 hydrolysis) and free intracellular Ca 2+ (Sakai et al, 1997;Oancea and Meyer, 1998;Shirai et al, 1998;Violin et al, 2003). In addition to triggering specific cellular inductive responses, intracellular Ca 2+ concentrations can affect the general state of the cell, for example the levels of protein synthesis and folding (Roderick et al, 2003b) and the decision to undergo apoptosis (Berridge et al, 1998). A review of other known Ca 2+ -sensitive factors can be found in Ikura et al, (2002).…”

Section: Effectors and Interpretation Of Calcium Signalsmentioning

confidence: 99%

Calcium signaling in vertebrate embryonic patterning and morphogenesis

Slusarski

Pelegri

2007

Developmental Biology

143

110

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Signaling pathways that rely on the controlled release and/or accumulation of calcium ions are important in a variety of developmental events in the vertebrate embryo, affecting cell fate specification and morphogenesis. One such major developmentally important pathway is the Wnt/calcium signaling pathway, which, through its antagonism of Wnt/beta-catenin signaling, appears to regulate the formation of the early embryonic organizer. In addition, the Wnt/calcium pathway shares components with another non-canonical Wnt pathway involved in planar cell polarity, suggesting that these two pathways form a loose network involved in polarized cell migratory movements that fashion the vertebrate body plan. Furthermore, left-right axis determination, neural induction and somite formation also display dynamic calcium release, which may be critical in these patterning events. Finally, we summarize recent evidence that propose a role for calcium signaling in stem cell biology and human developmental disorders.

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The Endoplasmic Reticulum: A Central Player in Cell Signalling and Protein Synthesis

Cited by 2 publications

References 97 publications

Calcium Signals Driven by Single Channel Noise

Calcium Signals Driven by Single Channel Noise

Calcium signaling in vertebrate embryonic patterning and morphogenesis

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