Sorting Nexins – Unifying Trends and New Perspectives

Abstract

The sorting nexins (SNXs) are a family of PX domaincontaining proteins found in yeast and mammalian cells that have been proposed to regulate intracellular trafficking. Mammalian SNXs have been suggested to function variously in pro-degradative sorting, internalization, endosomal recycling, or simply in endosomal sorting. In yeast, the defining function for these proteins is a regulation of cargo retrieval. Here we examine recent data on the SNX family of proteins and attempt to draw out unifying themes between the work performed in yeast and mammalian systems.

A Retromerlike Complex Is a Novel Rab7 Effector That Is Involved in the Transport of the Virulence Factor Cysteine Protease in the Enteric Protozoan ParasiteEntamoeba histolytica

“…One should be cautious to interpret data of knockdown and overexpression experiments because they often contradict. It was shown by siRNA that knockdown of SNX1 showed no effect on EGF receptor degradation (Gullapalli et al, 2004;Carlton et al, 2004) or on transferrin receptor trafficking (Carlton et al, 2004), whereas SNX1 is required for proper endosome retrieval of the CI-MPR (Carlton et al, 2005). This contrasts with the findings of previous studies using overexpression showing that overexpression of SNX1 enhances EGF receptor degradation (Kurten et al, 1996;Chin et al, 2001;Zheng et al, 2001), whereas other groups were unable to demonstrate that overexpression of SNX1 or SNX2, 3, or 4 increases the turnover of insulin or EGF receptors (Haft et al, 1998).…”

Interaction of the Wiskott–Aldrich syndrome protein with sorting nexin 9 is required for CD28 endocytosis and cosignaling in T cells

“…The PtdIns phosphate-binding SNX PX domains bind to specific phospholipids so as to target individual nexins to specific membranous sites (27,28). To explore the relevance of SNX9 interaction with WASp, we examined the PtdIns-binding properties of SNX9 by probing nitrocellulose-immobilized PtdIns arrays with GST SNX9 PX domain fusion protein and immunoblotting with anti-GST antibody.…”

“…Sorting nexins are a family of peripheral membrane proteins involved in endocytosis, membrane trafficking, and protein sorting (27,28) and defined by a phox (phagocyte oxidase) homology domain (PX) that mediates binding to PtdIns phosphates and consequent targeting to PtdIns-enriched membrane sites. SNX9 has been studied in human, murine, and Drosophila cells and binds directly to AP-2, clathrin, dynamin-2, Drosophila orthologue of Nck, and activated cdc42-associated kinase, localizes at the curved site of clathrin-coated pits, and modulates membrane trafficking of dynamin and clathrin-mediated endocytosis/sorting of several transmembrane receptors (29)(30)(31)(32)(33).…”

Essential role of RGS-PX1/sorting nexin 13 in mouse development and regulation of endocytosis dynamics

“…Trafficking between these endocytic compartments is highly regulated and often involves critical sorting steps. Recently, a large family of sorting nexin (SNX) proteins characterized by the presence of Phox (PX) domains has been identified and implicated in the regulation of different steps of the endocytic pathway (4,5). For example, the founding member of the SNX family, SNX1, was identified as an interacting partner of the epidermal growth factor receptor, and overexpression of SNX1 was found to enhance lysosomal degradation of epidermal growth factor receptor (6).…”