Messenger-specific role for nicotinic acid adenine dinucleotide phosphate in neuronal differentiation.
Cells possess several Ca2+-mobilizing messengers, which couple stimulation at the cell surface by a multitude of extracellular cues to the regulation of intracellular Ca2+-sensitive targets. Recent studies suggest that agonists differentially select from this molecular palette to generate their characteristic Ca2+ signals but it is still unclear whether different messengers mediate different functions or whether they act in a redundant fashion. In this study, we compared the effects of nicotinic acid adenine dinucleotide phosphate (NAADP), a novel Ca2+-mobilizing messenger, with that of the prototypical messenger inositol trisphosphate on cytosolic Ca2+ levels and differentiation status of PC12 cells. We demonstrate that liposomal delivery of NAADP mediated release of Ca2+ from acidic Ca2+ stores and that this stimulus was sufficient to drive differentiation of the cells to a neuronal-like phenotype. In sharp contrast, cell fate was unaffected by more transient Ca2+ signals generated by inositol trisphosphate-evoked release of endoplasmic reticulum Ca2+ stores. Our data establish for the first time (i) the presence of novel NAADP-sensitive Ca2+ stores in PC12 cells, (ii) a role for NAADP in differentiation, and (iii) that Ca2+-dependent function can be messenger-specific. Thus, differential recruitment of intracellular Ca2+-mobilizing messengers and their target Ca2+ stores may represent a robust means of maintaining stimulus fidelity in the control of Ca2+-dependent cell function.
Brailoiu
Eugen
E
Department of Pharmacology, Temple University Medical School, Philadelphia, Pennsylvania, USA.
Churamani
Dev
D
Pandey
Vinita
V
Brailoiu
G Cristina
GC
Tuluc
Florin
F
Patel
Sandip
S
Dun
Nae J
NJ
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects*; D003600:Cytosol / Q000187:drug effects / Q000378:metabolism; D009249:NADP / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016716:PC12 Cells; D051381:Rats
D009249:NADP; C024376:NAADP; D002118:Calcium