Structure and composition of the postsynaptic density during development

Abstract

In this study, we used electron tomography as well as immuno-gold labeling to analyze the morphology and distribution of proteins within PSDs isolated from rats before birth (embryonic day 19) and at post-natal days 2, 21 and 60. Our data provides direct evidence of distinct morphological and compositional differences in PSDs throughout development. Not all PSD components are present at the early stages of development, with a near lack of the scaffolding molecule PSD-95 at E19 and P2. The presence of NR1 and NR2b suggests that PSD-95 is not directly required for clustering of N-methyl-D-aspartic acid (NMDA) receptors in PSDs early in development. α-Actinin is abundant by E19 suggesting it is a core structural component of the PSD. Both α and β isoforms of Ca 2+ /calmodulin-dependent protein kinase II (CaMKII) are present early on, but then rise in labeling density approximately four-fold by P21. Of all the molecules studied, only calmodulin (CaM) was found in higher abundance early in PSD development and then fell in amount over time. Spatial analysis of the immuno-gold label shows a non-random distribution for all the proteins studied, lending support to the idea that the PSD is systematically assembled in an organized fashion. Morphological data from electron tomography shows that the PSD undergoes major structural changes through out development.

Ultrastructure of Synapses in the Mammalian Brain

“…6A,B) (Sans et al 2000;Valtschanoff et al 2000;Valtschanoff and Weinberg 2001) and are fairly uniformly distributed tangentially along the synaptic membrane, except for SAP97, which concentrates at the edge of the synapse and is thought to interact selectively with the AMPAR subunit GluA1. Recent results using the immunogold-PSD technique confirm these conclusions within the isolated PSD (DeGiorgis et al 2006;Swulius et al 2010). PSD-95 was originally thought to play a special role in anchoring NMDARs, but more recent evidence suggests that PSD-95 may be at least as important in regulating the surface expression of AMPARs (Schnell et al 2002;Ehrlich and Malinow 2004).…”

Local palmitoylation cycles define activity-regulated postsynaptic subdomains

“…4 G, red dashed curves). A similar size distribution had been previously described for PSDs in an electron microscopic analysis (Arellano et al, 2007;Swulius et al, 2010). It is conceivable that the PF11-labeled postsynaptic structure may represent the PSD, and that the PSD may be composed by a set of palmitoylated PSD-95-enriched subdomains with diameters of 200 nm.…”

The Postsynaptic Organization of Synapses

“…The structure and composition of PSDs change during maturation of synapses (Petralia et al 2005;Swulius et al 2010). Expression levels of many PSD proteins (e.g., PSD-95, CaMKIIa, and AMPA receptor subunits) increase during development, reaching their peaks at 2-4 wk after birth and correlating with the formation and maturation of synapses in the brain (Sans et al 2000;Petralia et al 2005).…”