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Our lab is interested in understanding the unprecedented susceptibility to schizophrenia associated with hemizygous deletions of the 22g11. 2 locus. We generate mouse models of genetic disruptions in this region to dissect the contributions of the twenty-seven genes identified as critical to disease risk within this 3 Mb locus. One of these genes, a neuronal palmitoyltransferase known as ZDHHC8, is an especially interesting candidate to examine because of its potential to dynamically impact the trafficking and function of its substrates by mediating the attachment of a labile and reversible lipid moiety. We used a transient overexpression system in HEK293 cells to initially identify PSD-95 as a substrate of ZDHHC8 palmitoyltransferase activity, and to demonstrate ZDHHC8 palmitoylation-dependent changes in the subcellular localization and membrane-association of PSD-95 in HEK293 cells. Subsequent …