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cc-by (c) Sindreu Balet, Carlos et al., 2014
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/108942

Zinc Transporter-1 Concentrates at the Postsynaptic Density of Hippocampal Synapses

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BACKGROUND: Zinc concentrates at excitatory synapses, both at the postsynaptic density and in a subset of glutamatergic boutons. Zinc can modulate synaptic plasticity, memory formation and nociception by regulating transmitter receptors and signal transduction pathways. Also, intracellular zinc accumulation is a hallmark of degenerating neurons in several neurological disorders. To date, no single zinc extrusion mechanism has been directly localized to synapses. Based on the presence of a canonical PDZ I motif in the Zinc Transporter-1 protein (ZnT1), we hypothesized that ZnT1 may be targeted to synaptic compartments for local control of cytosolic zinc. Using our previously developed protocol for the co-localization of reactive zinc and synaptic proteins, we further asked if ZnT1 expression correlates with presynaptic zinc content in individual synapses. FINDINGS: Here we demonstrate that ZnT1 is a plasma membrane protein that is enriched in dendritic spines and in biochemically isolated synaptic membranes. Hippocampal CA1 synapses labelled by postembedding immunogold showed over a 5-fold increase in ZnT1 concentration at synaptic junctions compared with extrasynaptic membranes. Subsynaptic analysis revealed a peak ZnT1 density on the postsynaptic side of the synapse, < 10 nm away from the postsynaptic membrane. ZnT1 was found in the vast majority of excitatory synapses regardless of the presence of vesicular zinc in presynaptic boutons. CONCLUSIONS: Our study has identified ZnT1 as a novel postsynaptic density protein, and it may help elucidate the role of zinc homeostasis in synaptic function and disease.

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SINDREU BALET, Carlos, BAYÉS, Àlex, ALTAFAJ, Xavier, PÉREZ CLAUSELL, Jeús. Zinc Transporter-1 Concentrates at the Postsynaptic Density of Hippocampal Synapses. _Molecular Brain_. 2014. Vol. 7, núm. 1, pàgs. 16-22. [consulta: 28 de gener de 2026]. ISSN: 1756-6606. [Disponible a: https://hdl.handle.net/2445/108942]

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