Questions and Controversies in Zinc Signaling
27 January 2004
The discovery, many years ago, of zinc in the synaptic vesicles of some glutamatergic neurons--as well as various other secretory vesicles--inaugurated a lively and at times controversial field concerning the normal physiological role of the sequestered zinc, its involvement in neurodegeneration and excitotoxic cell death and in epilepsy, and the mechanisms whereby zinc achieves both its physiological and its pathological effects (see Frederickson). Among the various possible functions of synaptic zinc, one of the most fascinating is the notion that zinc released from presynaptic nerve terminals crosses the synapse to not only affect various channels and receptors but to enter the post-synaptic cell and modulate the activity of various signaling pathways (see Perspective by Li et al.). In contrast to this view, a recent article makes the provocative suggestion that, rather then being freely released into the synapse, the zinc associated with synaptic vesicles may be externalized to act as a "hook" for extracellular zinc-binding molecules (Kay).
Zinc has many functions far from the synapse, of course, and is well known for playing a structural role in stabilizing the zinc fingers found in many transcription factors and various signaling proteins. The recent observation that zinc fingers may act as sensors to regulate activation domain function of the yeast transcription factor Zap 1 (Bird et al.) adds a new twist to the role of these nucleic acid-binding domains. The observation that activation of protein kinase C (PKC) through two distinct pathways led to an increase in free intracellular zinc traced to the zinc finger domains of PKC and the intriguing suggestion that, far from playing a static role in stabilizing the zinc finger domain, zinc serves as "the linchpin that orchestrates dynamic changes in response to specific signals" in PKC activation (Korichneva et al.).
Feel free to raise questions related to zinc signaling, or to comment on any of the research discussed above--or on any other aspects of the zinc signaling field.
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