Assembling microtubules disintegrate the postsynaptic density in vitro

The postsynaptic density (PSD), a disk-shaped protein aggregation of several hundred nm in diameter, plays important roles in the signal transduction and molecular organization of the excitatory synapses in mammalian CNS. The PSD resides in the microfilament-enriched cytoplasm of dendritic spines where the transient appearance of microtubules has been reported. When PSD isolated from porcine brain was incubated with polymerizing alpha,beta-tubulins, its turbidity became greater than that of the original PSD, suggesting that the PSD's structure was altered upon incubating with assembling microtubules. By transmission electron microscopy, smaller PSD fragments and several novel structures, including holes and finger-like extensions, were found in the PSD after incubation with assembling microtubules, but not in the original PSD or in the PSD incubated with alpha,beta-tubulins pretreated with vincristine. The results suggest that the interactions with assembling microtubules may result in the formation of holes in the PSD, and the rupture of these holes subsequently leads to the formation of smaller PSD fragments.