Zn2+ transporters and Zn2+ homeostasis in neurons
Section snippets
The Zn2+-containing cell: unifying concepts in Zn2+ transport and homeostasis
This review will combine old and new research findings addressing Zn2+ biology, building a conceptual framework describing our understanding of Zn2+ homeostasis in the neuron and the role played by Zn2+ transporters. We will certainly focus on new and exciting findings, areas of controversy, and will try to highlight gaps in our knowledge. Our first task will describe briefly the role Zn2+ plays in the nervous system and why Zn2+ homeostasis is important. Zn2+ is an essential trace element
What are the resting intracellular and extracellular concentrations of free Zn2+ in the brain?
The amount of Zn2+ in the mammalian brain averages about 10 μg/g (wet weight) and is fairly uniform over different regions or when comparing the grey and white matter (Frederickson, 1989). Although interesting developmental changes in brain Zn2+ occur, little change in total brain Zn2+ is observed with aging (Frederickson, 1989). Presumably then, the total amount of Zn2+ in the extracellular fluid and cytosol is fairly constant throughout the brain. Zn2+ concentration in the serum and
Zinc transporters: several different zinc transporter families have been identified; each family probably has a unique transport mechanism, function, and cellular location
In eukaryotic organisms, three families of metal cation transporters have now been identified and well characterized and others are certainly yet to be discovered. Most studies of the identification and functional characterization of these transporters have not been done in neurons, but what we do know from functional studies and expression analysis in brain suggests that these transporters are present in neurons and function in ways similar to those better characterized in other eukaryotic
ZnT transporters
Whereas ZnT-1 has ubiquitous expression (including the brain), the other ZnT family members show tissue-specific expression. We know little about the factors that control the tissue-specific transcriptional regulation of ZnT family members. It appears that ZnT-1, -3, -4, -5, -6, and hZTL1 are expressed in the brain. The transcriptional regulation and the control of the cellular localization of the various ZnT transporters expressed in the brain are probably complex, but by analogy with simpler
Summary
A better understanding of neuronal Zn2+ homeostasis and Zn2+ transporters will be critical for defining not only the role(s) played by Zn2+ in cell signaling, but also the role Zn2+ plays in neurodegenerative human diseases. Much has been learned in the last 10 years, but much more is still to be discovered. Now is an exciting time to be involved in Zn2+ research. This review presents a working model of neuronal Zn2+ homeostasis, which is most notable for the number of question marks contained
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