Study Identifies Conserved Molecular Pathway Controlling Clearance of Apoptotic Cells
Researchers using genome-wide screening in C. elegans identified a signaling pathway where the engulfment receptor CED-1 activates the adhesion GPCR LAT-1 to promote the degradation of apoptotic cells through phagosome maturation. This pathway involves a cascade of proteins (Gs/adenylyl cyclase/PKA/AST-1) that triggers transcription of genes essential for clearing dead cells. The findings are significant because the pathway is evolutionarily conserved across species and may explain defects in diseases like autoimmunity and neurodegeneration.
A new study published on bioRxiv describes the discovery of a conserved molecular pathway controlling efferocytosis—the clearance of apoptotic cells—which is essential for tissue homeostasis and preventing inflammation. Using a genome-wide RNAi screen in the nematode C. elegans, researchers identified the adhesion G protein-coupled receptor LAT-1 as a key regulator that promotes phagosome maturation during apoptotic cell degradation. Further screening revealed that the transcription factor AST-1 acts downstream of LAT-1 in this process. The researchers demonstrated that the engulfment receptor CED-1 functions as a ligand for LAT-1, triggering a signaling cascade involving Gs protein, adenylyl cyclase, and protein kinase A that ultimately activates AST-1 to induce transcription of genes encoding phosphatidylinositol 3-kinases. Importantly, this pathway is evolutionarily conserved, with functional homologs identified in fruit flies (CIRL) and mammals (ADGRL3), suggesting the mechanism may be relevant to human biology and disease.
Limitations & open questions
The study's own limitations are not detailed in the abstract provided, such as whether findings have been validated in mammalian systems, potential off-target effects of RNAi screening, or the scope of diseases examined in relation to pathway dysfunction.
What different sources said
- bioRxivCenter
The engulfment receptor CED-1/MEGF10 activates the GPCR LAT-1/ADGRL3 for apoptotic cell degradation
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