Distinct domains within PSD-95 mediate synaptic incorporation, stabilization, and activity-dependent trafficking.

摘要: The postsynaptic density (PSD) consists of a lattice-like array interacting proteins that organizes and stabilizes receptors, ion channels, structural, signaling necessary for synaptic function. To study the stabilization within this structure contribution these to integrity PSD, we tagged with PAGFP (photoactivatable green fluorescent protein) used combined two-photon laser-scanning microscopy laser photoactivation measure their rate turnover in individual spines rat CA1 pyramidal neurons. We find PSD-95 is highly stable spine, more so than other PSD-associated such as CaMKIIalpha, CaMKIIbeta, GluR2, Stargazin. Analysis series mutants revealed distinct domains stabilize PSD contribute formation. Stabilization requires N-terminal palmitoylation protein interactions mediated by first second PDZ domains, whereas formation lattice molecules additionally C-terminal SH3 domain. Furthermore, domain 1 2 dependent manner, activation NMDA receptors chemical long-term depression protocol rapidly destabilizes causes subset previously anchored spine be released. Thus, through analysis rates exchange PSD-95, determine separate play specific roles establishing lattice, allowing enter reorganizing response plasticity-inducing stimuli.