Calcium fingerprints induced by calmodulin interactors in eukaryotic cells.
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.
Dagher
Rania
R
UMR CNRS 7200, Université de Strasbourg, Faculté de Pharmacie 74, route du Rhin, F-67401 Illkirch, France.
Brière
Christian
C
Fève
Marie
M
Zeniou
Maria
M
Pigault
Claire
C
Mazars
Christian
C
Chneiweiss
Hervé
H
Ranjeva
Raoul
R
Kilhoffer
Marie-Claude
MC
Haiech
Jacques
J
D016880:Anisotropy; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002460:Cell Line; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000378:metabolism; D005057:Eukaryotic Cells / Q000378:metabolism*; D006801:Humans; D007093:Imidazoles / Q000737:chemistry / Q000378:metabolism; D015394:Molecular Structure; D013050:Spectrometry, Fluorescence; D013449:Sulfonamides / Q000737:chemistry / Q000378:metabolism; D014026:Nicotiana
D002147:Calmodulin; D004791:Enzyme Inhibitors; D007093:Imidazoles; D013449:Sulfonamides; C040184:W 12; C031938:calmidazolium; C036596:bifonazole; D002118:Calcium