PTP zeta/RPTP beta is a proteoglycan-type receptor-like protein tyrosine ph
osphatase specifically expressed in the brain. Although several ligands of
PTP zeta have been identified, proteins interacting with the intracellular
region of PTP zeta are still unknown. We performed yeast two-hybrid screeni
ng using the intracellular region of PTP zeta as a bait, and found that the
C-terminal sequence of PTP zeta binds to the PSD-95/SAP90 family through t
he second PDZ domain. Immunohistochemical analysis revealed that PTP zeta a
nd PSD-95/SAP90 are similarly distributed in the dendrites of pyramidal neu
rons of the hippocampus and neocortex. Furthermore, subcellular fractionati
on experiments indicated that PTPS is concentrated in the postsynaptic dens
ity fraction. These results suggested that PTPS is involved in the regulati
on of synaptic function as postsynaptic macromolecular complexes with PSD-9
5/SAP90. (C) 1999 Elsevier Science B.V. All rights reserved.