Protein components of post-synaptic density lattice, a backbone structure for type I excitatory synapses.

Area of Science:

• Neuroscience
• Molecular Biology
• Cell Biology

Background:

• The molecular architecture of the post-synaptic density (PSD) is crucial for understanding synaptic plasticity.
• Existing models primarily focus on scaffolding proteins, but the role of the 'PSD lattice' remains unclear.

Purpose of the Study:

• To investigate the molecular composition of the PSD lattice.
• To elucidate the relationship between the PSD lattice and scaffold protein models.
• To propose a novel model for PSD molecular architecture.

Main Methods:

• Purification of PSD lattice fractions from rat forebrain synaptic plasma membranes.
• Immuno-gold negative staining electron microscopy to identify protein components.
• Analysis of PSD composition in both adult and juvenile rat brains.

Main Results:

• Tubulin, actin, α-internexin, and Ca2+/calmodulin-dependent kinase II were identified as major constituents of the PSD lattice.
• Scaffolding proteins (PSD-95, SAP102, GKAP, Shank1, Homer) were found to be minor components.
• Similar PSD lattice structures were observed in both adult and 7-day-old rat brains.

Conclusions:

• A 'PSD lattice-based dynamic nanocolumn' model is proposed, integrating scaffold and lattice protein roles.
• Cytoskeletal proteins, particularly tubulin, actin, and α-internexin, are proposed as major contributors to the PSD backbone.
• The model suggests cytoskeletal proteins provide essential linker sites for PSD scaffold protein complexes.