Neuropeptide INS-14 modulates apoptotic cell clearance in Caenorhabditis elegans

Apoptosis, a principal form of programmed cell death, is integral to animal development. Neuropeptides, which are crucial signaling molecules in the nervous system, play roles in various physiological and behavioral processes. Until now, there has been no evidence of neuropeptides being involved in the clearance of apoptotic cells. Consequently, utilizing Caenorhabditis elegans-an exemplary model organism for investigating apoptosis and its regulatory mechanisms-we performed a comprehensive functional screening of neuropeptide genes via RNA interference (RNAi) technology to identify pivotal neuropeptide genes involved in apoptosis and apoptotic cell clearance. C. elegans possesses 113 neuropeptide genes. Our screening identified 9 neuropeptide genes as preliminary regulators of apoptosis, with 2 neuropeptide genes specifically involved in apoptotic cell clearance. Among these, the neuropeptide gene ins-14 exhibited the most significant regulatory phenotype. Further mechanistic investigations revealed that, during the late stage of apoptotic cell clearance, disruptions in ins-14 function markedly affect the recruitment efficiency of the key protein LAAT-1 to phagosomes and disrupt the normal acidification process within phagosomes. Moreover, we found that ins-14 modulated laat-1 expression at the transcriptional level. This study is the first to elucidate the regulatory role of neuropeptides in apoptotic cell clearance in C. elegans, offering novel experimental evidence for a more profound understanding of neuropeptide-mediated apoptotic regulatory networks.