TY - JOUR
T1 - Cypin
T2 - A cytosolic regulator of PSD-95 postsynaptic targeting
AU - Firestein, Bonnie L.
AU - Brenman, Jay E.
AU - Aoki, Chiye
AU - Sanchez-Perez, Ana M.
AU - Ei-Husseini, Alaa El Din
AU - Bredt, David S.
N1 - Funding Information:
The authors thank Joshua F. Kilbridge, Alice Elste, Mary Chan, and Joel Rosen for excellent technical assistance; Sarah E. Craven for insightful discussions; and Elizabeth Bellochio for advice on synaptosomal fractionation. This work was supported by a National Institute for Child Health and Human Development National Research Service Award (B. L. F.); a Spinal Cord Research Foundation Postdoctoral Fellowship (B. L. F); an American Heart Association Predoctoral Fellowship (J. E. B.); a Human Frontier Science Program Award (C. A.); National Institutes of Health grants R01-EY08055 and R01-NS36017 (C. A. and D. S. B.); National Science Foundation grants RCD 92-53750 and 94015013 (C. A. and D. S. B.); and by additional grants from the New York University Research Challenge Fund (C. A.), the EJLB (D. S. B.), and the Culpeper and Beckman Foundations (D. S. B.).
PY - 1999/11
Y1 - 1999/11
N2 - Postsynaptic density 95 (PSD-95/SAP-90) is a membrane associated guanylate kinase (GK) PDZ protein that scaffolds glutamate receptors and associated signaling networks at excitatory synapses. Affinity chromatography identifies cypin as a major PSD-95-binding protein in brain extracts. Cypin is homologous to a family of hydrolyric bacterial enzymes and shares some similarity with collapsin response mediator protein (CRMP), a cytoplasmic mediator of semaphorin III signalling. Cypin is discretely expressed in neurons and is polarized to basal membranes in intestinal epithelial cells. Overexpression of cypin in hippocampal neurons specifically perturbs postsynaptic trafficking of PSD-95 and SAP-102, an effect not produced by overexpression of other 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.
AB - Postsynaptic density 95 (PSD-95/SAP-90) is a membrane associated guanylate kinase (GK) PDZ protein that scaffolds glutamate receptors and associated signaling networks at excitatory synapses. Affinity chromatography identifies cypin as a major PSD-95-binding protein in brain extracts. Cypin is homologous to a family of hydrolyric bacterial enzymes and shares some similarity with collapsin response mediator protein (CRMP), a cytoplasmic mediator of semaphorin III signalling. Cypin is discretely expressed in neurons and is polarized to basal membranes in intestinal epithelial cells. Overexpression of cypin in hippocampal neurons specifically perturbs postsynaptic trafficking of PSD-95 and SAP-102, an effect not produced by overexpression of other 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.
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U2 - 10.1016/s0896-6273(00)81120-4
DO - 10.1016/s0896-6273(00)81120-4
M3 - Article
C2 - 10595517
AN - SCOPUS:0033230859
SN - 0896-6273
VL - 24
SP - 659
EP - 672
JO - Neuron
JF - Neuron
IS - 3
ER -