▪ Abstract PDZ domains are modular protein interaction domains that bind in a sequence-specific fashion to short C-terminal peptides or internal peptides that fold in a β-finger. The diversity of PDZ binding specificities can be explained by variable amino acids lining the peptide-binding groove of the PDZ domain. Abundantly represented in Caenorhabditis elegans, Drosophila melanogaster, and mammalian genomes, PDZ domains are frequently found in multiple copies or are associated with other protein-binding motifs in multidomain scaffold proteins. PDZ-containing proteins are typically involved in the assembly of supramolecular complexes that perform localized signaling functions at particular subcellular locations. Organization around a PDZ-based scaffold allows the stable localization of interacting proteins and enhances the rate and fidelity of signal transduction within the complex. Some PDZ-containing proteins are more dynamically regulated in distribution and may also be involved in the trafficking of interacting proteins within the cell.

The introduction of high-resolution time lapse imaging and molecular biological tools has changed dramatically the rate of progress towards the understanding of the complex structure-function relations in synapses of central spiny neurons. Standing issues, including the sequence of molecular and structural processes leading to formation, morphological change, and longevity of dendritic spines, as well as the functions of dendritic spines in neurological/psychiatric diseases are being addressed in a growing number of recent studies. There are still unsettled issues with respect to spine formation and plasticity: Are spines formed first, followed by synapse formation, or are synapses formed first, followed by emergence of a spine? What are the immediate and long-lasting changes in spine properties following exposure to plasticity-producing stimulation? Is spine volume/shape indicative of its function? These and other issues are addressed in this review, which highlights the complexity of molecular pathways involved in regulation of spine structure and function, and which contributes to the understanding of central synaptic interactions in health and disease.