SORTING NEXIN 3 REGULATES PHAGOCYTOSIS AND CROSS-PRESENTATION IN DENDRITIC CELLS

Abstract

Dendritic cells (DC) are the key cell type that carries out phagocytosis and cross-presentation. A well-regulated membrane/protein trafficking network is integral to phagocytosis and cross-presentation. Sorting nexin 3 (SNX-3) is an established regulator in membrane/protein trafficking. Intriguingly, the roles of SNX-3 along the phagocytic pathway and cross-presentation have not been investigated. Our results show that silencing of SNX-3 enhanced phagocytosis in DC. Furthermore, SNX-3 competes with a larger PI(3)P lipid-binding protein, EEA-1, in the recruitment to membranes. Hence, SNX-3 may negatively regulates phagocytosis in DC by modulating the recruitment of larger PI(3)P lipid-binding proteins such as EEA-1 to phagosomal membranes. In addition, SNX-3 knockdown DC showed an increase in surface expression of H-2K/D and H-2Kb/SIINFEKL that explained the increased cross-presentation in DC. Such modulation of MHC I and peptide-MHC I complexes (pMHC I) surface expression is likely linked to SNX-3¿s role in regulating phagocytosis and early endosomal sorting and recycling.