Amplification of Ca2+ signaling by diacylglycerol-mediated inositol 1,4,5-trisphosphate production.
Stimulation of various cell surface receptors leads to the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) through phospholipase C (PLC) activation, and the IP3 and DAG in turn trigger Ca2+ release through IP3 receptors and protein kinase C activation, respectively. The amount of IP(3) produced is particularly critical to determining the spatio-temporally coordinated Ca(2+)-signaling patterns. In this paper, we report a novel signal cross-talk between DAG and the IP3-mediated Ca(2+)-signaling pathway. We found that a DAG derivative, 1-oleoyl-2-acyl-sn-glycerol (OAG), induces Ca2+ oscillation in various types of cells independently of protein kinase C activity and extracellular Ca2+. The OAG-induced Ca2+ oscillation was completely abolished by depletion of Ca2+ stores or inhibition of PLC and IP3 receptors, indicating that OAG stimulates IP3 production through PLC activation and thereby induces IP3-induced Ca2+ release. Furthermore, intracellular accumulation of endogenous DAG by a DAG-lipase inhibitor greatly increased the number of cells responding to agonist stimulation at low doses. These results suggest a novel physiological function of DAG, i.e. amplification of Ca2+ signaling by enhancing IP3 production via its positive feedback effect on PLC activity.
Hisatsune
Chihiro
C
Laboratory for Developmental Neurobiology, RIKEN Brain Science Institute (BSI) 2-1 Hirosawa, Wako City, Saitama 351-0198, Japan. chihiro@brain.riken.jp
Nakamura
Kyoko
K
Kuroda
Yukiko
Y
Nakamura
Takeshi
T
Mikoshiba
Katsuhiko
K
D000818:Animals; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000502:physiology; D020013:Calcium Signaling; D006224:Cricetinae; D004075:Diglycerides / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000096:biosynthesis*; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear / Q000502:physiology; D010738:Type C Phospholipases / Q000502:physiology; D019061:src-Family Kinases / Q000502:physiology
C011439:1,2-diacylglycerol; D015220:Calcium Channels; D004075:Diglycerides; C506926:ITPR1 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D018160:Receptors, Cytoplasmic and Nuclear; D015544:Inositol 1,4,5-Trisphosphate; D019061:src-Family Kinases; D010738:Type C Phospholipases; D002118:Calcium