8,A,194. The Sorting Nexin (SNX) Family
SNX1 and other sorting nexins are involved in several stages of intracellular trafficking. It interacts with membranes containing phosphatidylinositol 3-phosphate (PtdIns(3P)) or phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2) (Cozier et al. 2002). It acts as a component of the retromer membrane-deforming SNX-BAR subcomplex (TC families 9.A.3 and 9.A 63). The SNX-BAR retromer mediates retrograde transport of cargo proteins from endosomes to the trans-Golgi network (TGN) and is involved in endosome-to-plasma membrane transport for cargo protein recycling. The SNX-BAR subcomplex functions to deform the donor membrane into a tubular profile called endosome-to-TGN transport carrier (ETC) and can sense membrane curvature; it has in vitro vesicle-to-membrane remodeling activity (Bhatia et al. 2009, van Weering et al. 2012). It is also involved in retrograde endosome-to-TGN transport of lysosomal enzyme receptors (IGF2R, M6PR and SORT1) and Shiginella dysenteria toxin, StxB. It plays a role in targeting ligand-activated EGFR to the lysosomes for degradation after endocytosis from the cell surface and release from the Golgi (Cozier et al. 2002, Kim et al. 2010). SNX1 interacts with SNX27 and regulates the heavy metal transporter Irt1 (TC# 2.A.5.1.2) (Chandra et al. 2022). Sorting nexins are also found in TC families 9.A.3 and 9.A.63.