Journal of Cell Biology 2007-05-21

Zinc is a novel intracellular second messenger.

Satoru Yamasaki, Kumiko Sakata-Sogawa, Aiko Hasegawa, Tomoyuki Suzuki, Koki Kabu, Emi Sato, Tomohiro Kurosaki, Susumu Yamashita, Makio Tokunaga, Keigo Nishida, Toshio Hirano

Index: J. Cell Biol. 177 , 637-45, (2007)

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Abstract

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.