As. Perez et Ds. Bredt, The N-terminal PDZ-containing region of postsynaptic density-95 mediates association with caveolar-like lipid domains, NEUROSCI L, 258(2), 1998, pp. 121-123
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 n
ecessary and sufficient to localize PSD-95 to caveolar-like domains. In tra
nsfected COS cells, a subpopulation of PSD-95 is buoyant in sucrose gradien
ts, and co-migrates with caveolin, a marker for caveolar domains. Sucrose g
radient separation of brain extracts showed that some neuronal PSD-95 prote
in 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 targe
ts PSD-95 to buoyant lipid domains remains unknown. PSD-95 does not interac
t with caveolin and palmitoylation of PSD-95 is not required for caveolar f
ractionation. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved.