Postsynaptic Targeting of MAGUKs Mediated by Distinct N-terminal Domains

Postsynaptic targeting of PSD-95 has been extensively studied; however, little is known about how other MAGUKs are localized. Proper targeting of PSD-95 requires dual palmitoylation of an N-terminal motif. We now find that the N-termini of closely related PSD-93 and SAP-102 are also involved in postsynaptic targeting. PSD-93 is N-terminally palmitoylated; however, unlike PSD-95, palmitoylation does not explain the necessity of the N-terminus for PSD-93 postsynaptic targeting. Furthermore, when the N-terminus of PSD-95 is replaced with the first 30 or 64, but not the first 10, amino acids of PSD-93, the chimera is targeted to postsynaptic sites independent of palmitoylation. Similarly, when the N-terminus of PSD-95 is replaced with the non-palmitoylated N-terminus of SAP-102, postsynaptic targeting is maintained. These results suggest that MAGUKs contain diverse signals within their N-termini for postsynaptic targeting.