Zinc transporter 3 (ZnT3) and vesicular zinc in central nervous system function |
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| Affiliation: | 1. Department of Otolaryngology, University of Pittsburgh, 3501 Fifth Avenue, Pittsburgh, PA 15261, USA;2. Department of Chemistry, Massachusetts Institute of Technology, 77 Massachusetts Avenue, Cambridge, MA 02139, USA;1. The Florey Institute for Neuroscience and Mental Health and The University of Melbourne, Parkville, Victoria 3052, Australia;2. Australian Synchrotron and the CSIRO Preventative Health Flagship, Clayton, Victoria 3168, Australia;3. Elemental Bio-imaging Centre, University of Technology Sydney, Broadway, New South Wales 2007, Australia;4. The Mental Health Research Institute, Parkville, Victoria 3052, Australia |
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| Abstract: | Zinc transporter 3 (ZnT3) is the sole mechanism responsible for concentrating zinc ions within synaptic vesicles in a subset of the brain’s glutamatergic neurons. This vesicular zinc can then be released into the synaptic cleft in an activity-dependent fashion, where it can exert many signaling functions. This review provides a comprehensive discussion of the localization and function of ZnT3 and vesicular zinc in the central nervous system. We begin by reviewing the fundamentals of zinc homeostasis and transport, and the discovery of ZnT3. We then focus on four main topics. I) The anatomy of the zincergic system, including its development and its modulation through experience-dependent plasticity. II) The role of zinc in intracellular signaling, with a focus on how zinc affects neurotransmitter receptors and synaptic plasticity. III) The behavioural characterization of the ZnT3 KO mouse, which lacks ZnT3 and, therefore, vesicular zinc. IV) The roles of ZnT3 and vesicular zinc in health and disease. |
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