Degradation of CNTNAP2 is mediated by both macroautophagy‐lysosome pathway and ubiquitin‐proteasome pathway

Background Recent studies suggested Contactin-associated protein-like 2 (CNTNAP2) as a novel risk gene for Alzheimer’s disease (AD). Reduced expression levels of CNTNAP2 were found in the brains AD patients. However, mechanisms underlying protein degradation remain elusive. Method HEK and N2a cells transfected with human plasmid treated cycloheximide, lysosome inhibitors, proteasome inhibitors. Immunoprecipitation was performed to study interaction between ubiquitin. Immunofluorescent staining investigate colocalization. Result Human has half-life approximately 4 hours. glycosylated mature form on cell membrane an intracellular immature form. Mature increased by inhibitors dose- time-dependent manner, while time-dependently. In addition, co-immunoprecipitated ubiquitin macroautophagy inhibitor 3-MA. further showed co-localization marker LAMP1. Conclusion is degraded via both pathways. Dysregulation ubiquitin-proteasome pathways have been implicated AD. Therefore, present may deepen current understanding pathogenesis.