Cypin: A cytosolic regulator of PSD-95 postsynaptic targeting

Postsynaptic density 95 (PSD-95/SAP-90) is a membrane associated guanylate kinase (GK) PDZ protein that scaffolds glutamate receptors and associated s ignaling networks at excitatory synapses. Affinity chromatography identifie s cypin as a major PSD-95-binding protein in brain extracts. Cypin is homol ogous to a family of hydrolytic bacterial enzymes and shares some similarit y with collapsin response mediator protein (CRMP), a cytoplasmic mediator o f semaphorin III signalling. Cypin is discretely expressed in neurons and i s polarized to basal membranes in intestinal epithelial cells. Overexpressi on of cypin in hippocampal neurons specifically perturbs postsynaptic traff icking of PSD-95 and SAP-102, an effect not produced by overexpression of o ther PDZ ligands. In fact, PSD-95 can induce postsynaptic clustering of an otherwise diffusely localized K+ channel, Kv1.4. By regulating postsynaptic protein sorting, cypin may influence synaptic development and plasticity.