PSD-95 Needs Binding Partner to Localize

Science's STKE  01 Dec 1999:
Vol. 1999, Issue 10, pp. tw3
DOI: 10.1126/stke.1999.10.tw3

Synaptic transmission requires activation of appropriate signal transduction cascades through a complex of proteins at the postsynaptic site. Organization of this signaling machinery involves members of the membrane-associated guanylate kinase (MAGUK) family, proteins that contain multiple protein-protein interaction domains. Postsynaptic density 95 (PSD-95) is a MAGUK that clusters glutamate receptors at postsynaptic sites and also binds to enzymes and ion channels that may participate in regulation of synaptic plasticity and neuronal development. Firestein et al. identified a protein in rat brain extract called cytoplasmic PSD-95 interactor (cypin), whose PDZ domain interacts with two PDZ domains of PSD-95. Cypin is expressed in specific neuron populations and cofractionated with synaptic plasma membrane and synaptic vesicles. When cypin was overexpressed in hippocampal neurons, localization of PSD-95 into clusters at postsynaptic sites was inhibited. The authors suggest that cypin is critical for postsynaptic trafficking of PSD-95. The similarity of cypin to certain hydrolytic bacterial enzymes indicates that it may also have catabolic activities critical to neuronal physiology.

Firestein, B.L., Brenman, J.E., Aoki, C., Sanchez-Perez, A.M., El-Husseini, A.E-D., and Bredt, D.S. (1999) Cypin: A cytosolic regulator of PSD-95 postsynaptic targeting. Neuron 24: 659-672. [Online Journal]