Calcium fingerprints induced by calmodulin interactors in eukaryotic cells.

Abstract

Calcium (Ca2+) is a ubiquitous second messenger which promotes cell responses through transient changes in intracellular concentrations. The prominent role of Ca2+ in cell physiology is mediated by a whole set of proteins constituting a Ca2+-signalling toolkit involved in Ca2+-signal generation, deciphering and arrest. The different Ca2+-signalosomes deliver Ca2+-signals with spatial and temporal dynamics to control the function of specific cell types. Among the intracellular proteins involved in Ca2+-signal deciphering, calmodulin (CaM) plays a pivotal role in controlling Ca2+-homeostasis and downstream Ca2+-based signalling events. Due to its ubiquitous expression in eukaryotic cells and the variety of proteins it interacts with, CaM is central in Ca2+-signalling networks. For these reasons, it is expected that disrupting or modifying CaM interactions with its target proteins will affect Ca2+-homeostasis and cellular responses. The resulting calcium response will vary depending on which interactions between CaM and target proteins are altered by the molecules and on the specific Ca2+-toolkit expressed in a given cell, even in the resting state. In the present paper, the effect of six classical CaM interactors (W5, W7, W12, W13, bifonazole and calmidazolium) was studied on Ca2+-signalling in tumor initiating cells isolated from human glioblastoma (TG1) and tobacco cells (BY-2) using the fluorescent Ca2+-sensitive Indo-1 dye and aequorin, respectively. Various Ca2+-fingerprints were obtained depending both on the CaM interactor used and the cell type investigated. These data demonstrate that interaction between the antagonists and CaM results in a differential inhibition of CaM-dependent proteins involved in Ca2+-signal regulation. In addition, the distinct Ca2+-fingerprints in tobacco and human tumor initiating glioblastoma cells induced by a given CaM interactor highlight the specificity of the Ca2+-signalosome in eukaryotic cells.

• Authors: Rania Dagher, Christian Brière, Marie Fève, Maria Zeniou, Claire Pigault, Christian Mazars, Hervé Chneiweiss, Raoul Ranjeva, Marie-Claude Kilhoffer, Jacques Haiech
• Journal: Biochimica et biophysica acta (Biochim Biophys Acta) Vol. 1793 Issue 6 Pg. 1068-77 (Jun 2009) ISSN: 0006-3002 [Print] Netherlands
• PMID: 19133300 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Calmodulin
• Enzyme Inhibitors
• Imidazoles
• Sulfonamides
• W 12
• calmidazolium
• bifonazole
• Calcium

Topics

• Anisotropy
• Calcium (metabolism)
• Calcium Signaling (physiology)
• Calmodulin (antagonists & inhibitors, metabolism)
• Cell Line
• Enzyme Inhibitors (chemistry, metabolism)
• Eukaryotic Cells (metabolism)
• Humans
• Imidazoles (chemistry, metabolism)
• Molecular Structure
• Spectrometry, Fluorescence
• Sulfonamides (chemistry, metabolism)
• Tobacco