Intracellular Ca(2+) release mechanisms: multiple pathways having multiple functions within the same cell type?
The elevation of the cytosolic and nuclear Ca(2+) concentration is a fundamental signal transduction mechanism in almost all eukaryotic cells. Interestingly, three Ca(2+)-mobilising second messengers, D-myo-inositol 1,4,5-trisphosphate (InsP(3)), cyclic adenosine diphosphoribose (cADPR), and nicotinic acid adenine dinucleotide phosphate (NAADP(+)) were identified in a phylogenetically wide range of different organisms. Moreover, in an as yet very limited number of cell types, sea urchin eggs, mouse pancreatic acinar cells, and human Jurkat T-lymphocytes, all three Ca(2+)-mobilising ligands have been shown to be involved in the generation of Ca(2+) signals. This situation raises the question why during evolution all three messengers have been conserved in the same cell type. From a theoretical point of view the following points may be considered: (i) redundant mechanisms ensuring intact Ca(2+) signalling even if one system does not work, (ii) the need for subcellularly localised Ca(2+) elevations to obtain a certain physiological response of the cell, and (iii) tight control of a physiological response of the cell by a temporal sequence of Ca(2+) signalling events. These theoretical considerations are compared to the current knowledge regarding the three messengers in sea urchin eggs, mouse pancreatic acinar cells, and human Jurkat T lymphocytes.
da Silva
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CP
University of Hamburg, University Clinic Hamburg-Eppendorf, Institute for Medical Biochemistry and Molecular Biology, Division of Cellular Signal Transduction, Grindelallee 117, D-20146, Hamburg, Germany.
Guse
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AH
D000246:Adenosine Diphosphate Ribose / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D005075:Biological Evolution; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D036563:Cyclic ADP-Ribose; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000235:genetics / Q000378:metabolism*; D009249:NADP / Q000031:analogs & derivatives* / Q000235:genetics / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction
D036563:Cyclic ADP-Ribose; D000246:Adenosine Diphosphate Ribose; D009249:NADP; C024376:NAADP; D015544:Inositol 1,4,5-Trisphosphate; D002118:Calcium