LC3-associated phagocytosis (LAP) (LAP)

LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway characterized by the recruitment of the autophagy protein LC3 to single-membrane phagosomes, known as LAPosomes [1, 4]. Unlike canonical macroautophagy, which sequesters intracellular components in double-membrane vesicles, LAP is triggered by the engagement of cell surface receptors like Toll-like receptors (TLRs) or Fc receptors during the engulfment of extracellular material [6, 10]. The pathway is molecularly distinct, requiring the protein Rubicon and reactive oxygen species (ROS) generated by NADPH oxidase 2 (NOX2), but it operates independently of the ULK1 initiation complex [4, 14]. LAP is essential for the immunologically silent clearance of apoptotic cells (efferocytosis) and the regulation of inflammatory signaling [4, 8]. Deficiencies in LAP are associated with the development of lupus-like autoimmune diseases due to the accumulation of uncleared cellular debris, while its activation in the tumor microenvironment can promote immune evasion by suppressing T-cell responses [4, 9]. Consequently, modulating LAP through its specific components, such as Rubicon or VPS34, represents a promising therapeutic strategy for treating inflammatory, autoimmune, and oncological conditions [1, 16]. Research into LAP has also identified its role in maintaining vision through the clearance of photoreceptor outer segments and in protecting against neurodegeneration by facilitating the clearance of protein aggregates [9, 11]. Therapeutic interventions currently focus on small molecule inhibitors of the VPS34 complex or lysosomal function to study and potentially treat LAP-associated pathologies [7, 13].

Other names

LC3-associated autophagyNon-canonical autophagyConjugation of ATG8 to single membranesCASMLANDO (LC3-associated endocytosis)

Modulation of the VPS34-containing PI3K complex, inhibition of NOX2-mediated ROS production, or disruption of lysosomal acidification and fusion