Architecture and assembly of scaffolded signaling complexes

Dynamic, scaffolded, multi-protein complexes are hallmarks of sophisticated cellular signaling systems. The higher-order architecture of these signaling complexes confers sensitivity, adaptability, control, and crosstalk. Signaling complex architecture is especially notable in the nervous system, where dynamic post-synaptic protein assemblies underlie the molecular origins of learning and memory.

Neuronal NO Signaling

The diatomic gas nitric oxide (NO) serves dual physiological roles as both a signaling molecule and an inflammation agent. Nitric oxide synthases (NOS) are large, multi-domain hemoproteins responsible for production of NO. Emitted at minute concentrations, NO is a membrane-permeable paracrine signaling agent. Generated at high levels, NO acts as a potent cytotoxic weapon of the immune system.

Post-Synaptic Density

Excitatory synapses exhibit characteristic proteinaceous microcompartments at the post-synaptic membrane known as the post-synaptic density (PSD). The PSD is richly organized into multi-protein complexes composed of glutamate receptors, scaffolding proteins, kinases, cytoskeleton, and G-protein signaling effectors. The dynamic reorganizations of the higher-order architecture and composition of PSD signaling complexes underlies synaptic plasticity, learning, and memory.