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Published online May 14, 2007
doi:10.1083/jcb.200702081
The Journal of Cell Biology, Vol. 177, No. 4, 637-645
The Rockefeller University Press, 0021-9525 $30.00
© 2007 Yamasaki et al.
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Article

Zinc is a novel intracellular second messenger



Satoru Yamasaki1, Kumiko Sakata-Sogawa2, Aiko Hasegawa1,6, Tomoyuki Suzuki1, Koki Kabu1,6, Emi Sato1,6, Tomohiro Kurosaki3, Susumu Yamashita6, Makio Tokunaga2,4,5, Keigo Nishida1,6, and Toshio Hirano1,6

1 Laboratory for Cytokine Signaling, 2 Research Unit for Single Molecule Immunoimaging, and 3 Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Yokohama, Kanagawa 230-0045, Japan
4 Structural Biology Center, National Institute of Genetics, and 5 Department of Genetics, The Graduate University for Advanced Studies, Shizuoka 411-8540, Japan
6 Laboratory of Developmental Immunology, Graduate School of Frontier Biosciences and Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan

Correspondence to Toshio Hirano: hirano{at}molonc.med.osaka-u.ac.jp

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 (Fc{varepsilon} receptor I [Fc{varepsilon}RI]) 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 Fc{varepsilon}RI-mediated signaling. Collectively, our findings indicate that zinc is a novel intracellular second messenger.

Abbreviations used in this paper: BMMC, bone marrow–derived mast cell; DTPA, diethylenetriaminepentaacetic acid; ERK, extracellular signal-regulated kinase; Fc{varepsilon}RI, Fc{varepsilon} receptor I; IL, interleukin; IP3R, inositol 1,4,5-triphosphate receptor; MEK, MAPK/ERK kinase; TIRF, total internal reflection fluorescence.


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