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.

Cryptogein, a fungal elicitor, remodels the phenylpropanoid metabolism of tobacco cell suspension cultures in a calcium‐dependent manner

“…By themselves, these drugs provoked changes in cellular calcium (Dagher et al . 2008) but in a differential manner (Fig.…”

Identification and Inhibitory Properties of a Novel Ca2+/Calmodulin Antagonist

“…Unlike binding of antagonists TFP and W-13 to CaM (34-35) (and Table 3S), binding of 125-C9 to CaM is not enthalpy driven, since ΔH binding is unfavorable, at least near room temperature. Instead, 125-C9 binding to CaM is driven by entropy, which suggests the interaction is due mostly to hydrophobic interactions.…”

Effects of external calcium on the biotransformation of ginsenoside Rb1 to ginsenoside Rd by Paecilomyces bainier 229-7

“…CaM is a calciumbinding protein expressed in all eukaryotic cells (Chin and Means 2000;Stevens 1983). CaM can detect free cytosolic calcium concentration and then transduce spatial and/or time modifications of the cytosolic calcium concentration into modulation of enzyme activities (Dagher et al 2009;Nelson et al 2004). As shown in Fig.…”

“…CaM acts a calcium sensor that can initiate Ca 2? signal transduction pathways and gene expression in various types of cells (Dagher et al 2009;White and Bancroft 1987). External Ca 2?…”