The N-terminal PDZ-containing region of postsynaptic density-95 mediates association with caveolar-like lipid domains.
Postsynaptic density-95 (PSD-95) is a palmitoylated peripheral membrane PDZ protein that organizes signaling molecules at synaptic sites. Here we find the amino terminal region of PSD-95, containing the three PDZ domains is necessary and sufficient to localize PSD-95 to caveolar-like domains. In transfected COS cells, a subpopulation of PSD-95 is buoyant in sucrose gradients, and co-migrates with caveolin, a marker for caveolar domains. Sucrose gradient separation of brain extracts showed that some neuronal PSD-95 protein is present in buoyant fractions as well. Analysis of truncated forms of the PSD-95 indicated that the N-terminal PDZ-containing region localizes to caveolae, but the C-terminal region, containing the SH3 and the guanylate kinase domains does not. The mechanism by which the N-terminal region targets PSD-95 to buoyant lipid domains remains unknown. PSD-95 does not interact with caveolin and palmitoylation of PSD-95 is not required for caveolar fractionation.
Perez
A S
AS
Department of Physiology, University of California at San Francisco School of Medicine, 94143-0444, USA.
Bredt
D S
DS
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D000818:Animals; D001665:Binding Sites; D019556:COS Cells; D051242:Caveolin 1; D022461:Caveolins; D002462:Cell Membrane / Q000378:metabolism*; D015870:Gene Expression; D008565:Membrane Proteins / Q000378:metabolism*; D008840:Microfilament Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D017384:Sequence Deletion; D013347:Subcellular Fractions / Q000378:metabolism; D014162:Transfection
D051242:Caveolin 1; D022461:Caveolins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009419:Nerve Tissue Proteins; C033652:postsynaptic density proteins