Structural role of zinc ions bound to postsynaptic densities

Abstract

Postsynaptic densities (PSDs) isolated from porcine cerebral cortices are large aggregates consisting of more than 30 different proteins. Inductively coupled plasma-mass spectrometric analyses revealed that isolated PSDs contained zinc at a concentration of 4.1 nmol per mg protein. Treatment with 8 M urea lead to dissociation of the PSDs into small components and, concomitantly, depletion of most of their bound zinc. After removal of the urea by dialysis, urea-dissociated PSD proteins did not reassemble into aggregates by themselves. Adding ZnCl 2 to urea-treated PSD samples resulted in the assembly of urea-dissociated proteins into large aggregates with morphology and protein composition closely resembling those of the original PSDs. Mg 2+ , Ca 2+ , Co 2+ , Cd 2+ , Cu 2+ , Mn 2+ , Fe 3+ , K + and Na + ions at higher concentrations also induced the aggregation of urea-dissociated PSD protein. The structures of the K + -, Na + -, Mg 2+ -and Ca 2+ -induced aggregates were distinct from that of the original PSDs. Our results indicate that the structure of the PSD could be disassembled and reassembled under in vitro conditions. They further suggest that Zn 2+ ions, by binding to certain zincbinding proteins, play an important role in the formation and maintenance of the structure of the PSD.

Scaffolding Proteins at the Postsynaptic Density: Shank as the Architectural Framework

“…Baron et al (2006) argued that the arraying capacity of the Shank SAM domains may provide a driving force in PSD assembly and that the Zn 2+ -dependent addition or removal of Shank monomers might contribute to structural plasticity of the postsynaptic scaffold (see also Gundelfinger et al 2006). Intriguingly, Jan et al (2002) have reported that Zn 2+ can trigger the reassembly of a denatured PSD preparation in vitro, further supporting the functional relevance of the SAM domain/Zn 2+ complex. Further self-association is provided by the PDZ domain, which, besides binding various membrane receptors and signaling proteins (see below), also has the capacity to form dimers, as observed in the high-resolution structure obtained from the Shank1 PDZ domain in complex with the PDZ ligand motif derived from GKAP/SAPAP (Im et al 2003).…”

Modulation of Neuronal Signal Transduction and Memory Formation by Synaptic Zinc

“…Biochemically isolated post-synaptic densities (PSD) contain a high amount of zinc (∼4 nmol/mg protein) that supports the structural organization of the PSD (Jan et al, 2002; Baron et al, 2006). Recent data indicate that at least a fraction of this zinc might be reactive or exchangeable, as it can be detected in association with Shank2/3 scaffold protein aggregates in dendritic spines with fluorescent zinc indicators (Grabrucker et al, 2011).…”

Brain-Delivery of Zinc-Ions as Potential Treatment for Neurological Diseases: Mini Review

“…Moreover, Zn 2+ is important for postsynaptic density (PSD) stability, such that PSDs contain a Zn 2+ concentration of 4.1 nmol per mg protein [31, 32]. Zn 2+ levels are also important for nucleic acid metabolism and brain microtubule growth [1].…”