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 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 hydrolytic 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.
Firestein
B L
BL
Department of Physiology, University of California, San Francisco 94143, USA.
Firestein
B L
BL
Brenman
J E
JE
Aoki
C
C
Sanchez-Perez
A M
AM
El-Husseini
A E
AE
Bredt
D S
DS
D000595:Amino Acid Sequence / Q000235:genetics; D000818:Animals; D001665:Binding Sites / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D005591:Chemical Fractionation; D003600:Cytosol / Q000502:physiology*; D000076122:Disks Large Homolog 4 Protein; D006148:Guanine Deaminase; D051528:Guanylate Kinases; D007413:Intestinal Mucosa / Q000166:cytology / Q000378:metabolism; D007425:Intracellular Membranes / Q000378:metabolism; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D009703:Nucleoside-Phosphate Kinase / Q000378:metabolism; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats / Q000196:embryology; D013569:Synapses / Q000378:metabolism / Q000502:physiology*
D002352:Carrier Proteins; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins; D009703:Nucleoside-Phosphate Kinase; D051528:Guanylate Kinases; C485728:Gda protein, rat; D006148:Guanine Deaminase