Extensions of PSD-95/discs large/ZO-1 (PDZ) domains influence lipid binding and membrane targeting of syntenin-1

Syntenin-1 is a PDZ protein involved in receptor recycling and clustering. Its two PDZ domains interact with various receptors and phosphoinositides, and are flanked by N- and C-terminal regions. Here, we report the identification of an autoinhibitory peptide stretch in the N-terminus that might be regulated by phosphorylation. We further establish that basic residues in the C-terminal region mediate electrostatic interactions with reconstituted liposomes and contribute to the plasma membrane targeting. Our study adds new components to the multi-dentate membrane targeting mechanism and highlights the role of N- and C-terminal PDZ extensions in the regulation of syntenin-1 plasma membrane localization.Structured summary of protein interactionsPDZ1-PDZ2 and peptidebind by fluorescence technology (View Interaction: 1, 2, 3, 4).

► The subcellular distribution of syntenin-1 is regulated by its N- and C-termini. ► A phosphorylation switch may regulate the N-terminal autoinhibition. ► The PDZ tandem and the C-terminus cooperate in membrane targeting of syntenin-1. ► Electrostatic interactions contribute to syntenin-1 membrane targeting.