Protein tyrosine phosphatase zeta/RPTPbeta interacts with PSD-95/SAP90 family.

PTPzeta/RPTPbeta is a proteoglycan-type receptor-like protein tyrosine phosphatase specifically expressed in the brain. Although several ligands of PTPzeta have been identified, proteins interacting with the intracellular region of PTPzeta are still unknown. We performed yeast two-hybrid screening using the intracellular region of PTPzeta as a bait, and found that the C-terminal sequence of PTPzeta binds to the PSD-95/SAP90 family through the second PDZ domain. Immunohistochemical analysis revealed that PTPzeta and PSD-95/SAP90 are similarly distributed in the dendrites of pyramidal neurons of the hippocampus and neocortex. Furthermore, subcellular fractionation experiments indicated that PTPzeta is concentrated in the postsynaptic density fraction. These results suggested that PTPzeta is involved in the regulation of synaptic function as postsynaptic macromolecular complexes with PSD-95/SAP90.