The synaptic protein PSD-95/SAP90 binds to and clusters a variety of m
embrane proteins via its two N-terminal PDZ domains. We report a novel
protein, CRIPT, which is highly conserved from mammals to plants and
binds selectively to the third PDZ domain (PDZ3) of PSD-95 via its C t
erminus. While conforming to the consensus PDZ-binding C-terminal sequ
ence (X-S/TX-V-COOH), residues at the -1 position and upstream of the
last four amino acids of CRIPT determine its specificity for PDZ3. In
heterologous cells, CRIPT causes a redistribution of PSD-95 to microtu
bules. In brain, CRIPT colocalizes with PSD-95 in the postsynaptic den
sity and can be coimmunoprecipitated with PSD-95 and tubulin. These fi
ndings suggest that CRIPT may regulate PSD-95 interaction with a tubul
in-based cytoskeleton in excitatory synapses.