Beyond self-eating: The control of nonautophagic functions and signaling pathways by autophagy-related proteins

Cadwell, Ken; Debnath, Jayanta

LAP serves as a host defense system targeting several pathogens, including Aspergillus fumigatus and Salmonella typhimurium (Huang et al., 2009; Martinez et al., 2015) and has emerged as a key regulator of inflammation and immunity. Previous studies have implicated autophagy in antigen presentation to T cells by major histocompatibility complex (MHC) molecules (Dengjel et al., 2005; Schmid et al., 2007) . However, optimal MHC-II presentation of peptides from phagocytosed pathogens requires LC3 targeting to phagosomes by ATGs and NOX2, suggesting that LAP mediates presentation of extracellularly derived antigens (Romao et al., 2013) . Importantly, LAP directs the production of type I IFN (IFN-I), namely IFN-α, in response to host-DNA containing immune complexes by plasmacytoid dendritic cells (Henault et al., 2012) . In addition to controlling the immune response, LAP is required for the phagocytosis and degradation of photoreceptor outer segments by retinal pigment epithelial cells in mice, which is essential for proper vision (Kim et al., 2013) . Overall, these studies reinforce the physiological importance of LAP as an autophagy-related pathway.