Zinc is a novel intracellular second messenger.
Zinc is an essential trace element required for enzymatic activity and for maintaining the conformation of many transcription factors; thus, zinc homeostasis is tightly regulated. Although zinc affects several signaling molecules and may act as a neurotransmitter, it remains unknown whether zinc acts as an intracellular second messenger capable of transducing extracellular stimuli into intracellular signaling events. In this study, we report that the cross-linking of the high affinity immunoglobin E receptor (Fcepsilon receptor I [FcepsilonRI]) induced a release of free zinc from the perinuclear area, including the endoplasmic reticulum in mast cells, a phenomenon we call the zinc wave. The zinc wave was dependent on calcium influx and mitogen-activated protein kinase/extracellular signal-regulated kinase kinase activation. The results suggest that the zinc wave is involved in intracellular signaling events, at least in part by modulating the duration and strength of FcepsilonRI-mediated signaling. Collectively, our findings indicate that zinc is a novel intracellular second messenger.
Yamasaki
Satoru
S
Laboratory for Cytokine Signaling, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa, Japan.
Sakata-Sogawa
Kumiko
K
Hasegawa
Aiko
A
Suzuki
Tomoyuki
T
Kabu
Koki
K
Sato
Emi
E
Kurosaki
Tomohiro
T
Yamashita
Susumu
S
Tokunaga
Makio
M
Nishida
Keigo
K
Hirano
Toshio
T
D000818:Animals; D002478:Cells, Cultured; D007424:Intracellular Fluid / Q000201:enzymology / Q000502:physiology*; D048748:MAP Kinase Kinase Kinase 3 / Q000378:metabolism; D008407:Mast Cells / Q000201:enzymology / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D017455:Receptors, IgE / Q000378:metabolism / Q000502:physiology; D015290:Second Messenger Systems / Q000502:physiology*; D015032:Zinc / Q000502:physiology*
D017455:Receptors, IgE; D048748:MAP Kinase Kinase Kinase 3; D015032:Zinc