DHHC-1-dependent modulation of CED-1 protein stability regulates apoptotic cell clearance in C. elegans

Dysregulation of apoptotic cell clearance is implicated in various diseases, including neurodegeneration and cancer. The phagocytic receptor CED-1 mediates the recognition of apoptotic cells by phagocytes and serves as a critical molecule for their clearance in C. elegans. However, the mechanisms ensuring the maintenance of optimal CED-1 protein levels for effective phagocytic function remain unclear. This study reveals that palmitoylation contributes to the clearance of apoptotic cells and identifies the palmitoyltransferase DHHC-1 as a key regulator of CED-1 protein levels in this process. The deletion of dhhc-1 led to a significant reduction in CED-1 protein levels, while its transcription was unaffected. Further analysis demonstrated that the absence of dhhc-1 resulted in a marked increase in the number of apoptotic cells, whereas overexpression of CED-1 restored this phenotype. Moreover, we found that DHHC-1 may stabilize CED-1 protein levels by preventing its degradation via the lysosomal and proteasomal pathways. Collectively, our findings reveal that DHHC-1 plays a vital role in the clearance of apoptotic cells by regulating CED-1 protein stability, underscoring the potential of targeting palmitoylation pathways in therapeutic strategies for diseases associated with defective apoptotic cell clearance.