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Protein S-palmitoylation, the addition of a long-chain fatty acid to target proteins, is among the most frequent reversible protein modifications in Metazoa, affecting subcellular protein localization, trafficking and protein-protein interactions. S-palmitoylated proteins are abundant in the neuronal system and are associated with neuronal diseases and cancer. Despite the importance of this post-translational modification, it has not been thoroughly studied in the model organism Drosophila melanogaster. Here we present the palmitoylome of Drosophila S2R+ cells, comprising 198 proteins, an estimated 3.5% of expressed genes in these cells. Comparison of orthologs between mammals and Drosophila suggests that S-palmitoylated proteins are more conserved between these distant phyla than non-S-palmitoylated proteins. To identify putative client proteins and interaction partners of the DHHC family of protein acyl-transferases (PATs) we established DHHC-BioID, a proximity biotinylation-based method. In S2R+ cells, ectopic expression of the DHHC-PAT dHip14-BioID in combination with Snap24 or an interaction-deficient Snap24-mutant as a negative control, resulted in biotinylation of Snap24 but not the Snap24-mutant. DHHC-BioID in S2R+ cells using 10 different DHHC-PATs as bait identified 520 putative DHHC-PAT interaction partners of which 48 were S-palmitoylated and are therefore putative DHHC-PAT client proteins. Comparison of putative client protein/DHHC-PAT combinations indicates that CG8314, CG5196, CG5880 and Patsas have a preference for transmembrane proteins, while S-palmitoylated proteins with the Hip14-interaction motif are most enriched by DHHC-BioID variants of approximated and dHip14. Finally, we show that BioID is active in larval and adult Drosophila and that dHip14-BioID rescues dHip14 mutant flies, indicating that DHHC-BioID is non-toxic. In summary we provide the first systematic analysis of a Drosophila palmitoylome. We show that DHHC-BioID is sensitive and specific enough to identify DHHC-PAT client proteins and provide DHHC-PAT assignment for ca. 25% of the S2R+ cell palmitoylome, providing a valuable resource. In addition, we establish DHHC-BioID as a useful concept for the identification of tissue-specific DHHC-PAT interactomes in Drosophila.

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Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that affects multiple organ systems. Many patients present with neurological and psychiatric signs and symptoms at some point in the course of the disease. Here, we present a patient with neuropsychiatric SLE (NPSLE) who presented with longstanding and difficult-to-control epileptic seizures and post-ictal psychotic symptoms prior to the diagnosis of SLE. A 39-year-old patient with a ten-year history of uncontrolled epileptic seizures despite multiple medications and recent diagnosis of chronic kidney disease presented to the emergency department following multiple witnessed seizures. Her seizures were controlled following initial interventions and the patient was admitted to the hospital to control metabolic acidosis and hyperkalemia. Later, the patient developed psychosis with auditory hallucinations, combative behavior, and agitation which were controlled with restraints and sedatives. Initial serological and urinary studies revealed disturbances of multiple systems and triggered broad workup resulting in positive serological SLE markers. The patient was then started on immunosuppressive medications with prompt control of post-ictal psychosis. The patient was discharged with immunosuppressive regimen and control of her seizures. This case highlights that signs and symptoms of NPSLE may appear before the onset of SLE diagnosis. Additionally, our patient had longstanding epilepsy with post-ictal psychosis, which has not been reported in the literature before. We believe this case highlights the challenges in the diagnosis of NPSLE, the rapid control of seizures and/or psychosis with SLE treatment, and the necessity to broaden the differential diagnosis in atypical presentation of seizures and/or psychosis.