ProSAP-interacting protein 1 (ProSAPiP1), a novel protein of the postsynaptic density that links the spine-associated rap-gap (SPAR) to the scaffolding protein ProSAP2/Shank3

ProSAPs/ Shanks are a family of proteins that have a major scaffolding function for components of the postsynaptic density ( PSD) of excitatory brain synapses. Members of the family harbor a variety of domains for protein- protein interactions, one of which is a unique PDZ domain that differs significantly from those of other proteins. We have identified a novel binding partner for this PDZ domain, termed ProSAPiP1, that is highly enriched in the PSD and shares significant sequence homology with the PSD protein PSDZip70. Both molecules code for a Fez1 domain that can be found in a total of four related proteins. ProSAPiP1 is widely expressed in rat brain and co- localizes with ProSAP2/ Shank3 in excitatory spines and synapses. ProSAP2/ Shank3 co- immunoprecipitates with ProSAPiP1 but not with PSD- Zip70. Both proteins, however, bind and recruit SPAR to synapses with a central coiled- coil region that harbors a leucine zipper motif. This region is also responsible for homo- and heteromultimerization of ProSAPiP1 and PSD- Zip70. Thus, ProSAPiP1 and PSD- Zip70 are founders of a novel family of scaffolding proteins, the Fezzins, which adds further complexity to the organization of the PSD protein network.