Paralog-specific intrabodies for PSD-93 and SAP102 expand the molecular toolkit to resolve excitatory synapse organization
A scarcity of live, paralog-specific tools has limited analysis of PSD-MAGUKs at excitatory synapses. To address this gap, we engineered small, 10FN3-derived binders that selectively recognize PSD-93 and SAP102 -alongside an enhanced PSD-95 reagent- and converted them into regulated, gene-encoded intrabodies for endogenous imaging. Through sequence-guided selection and targeted optimization, we obtained high-specificity reagents that label their native targets in neurons with minimal perturbation and support multiplexed live-cell and advanced imaging modalities. This toolkit enables differential visualization of MAGUK paralogs at native levels and provides a practical route to dissect their distinct contributions to synapse organization and plasticity.