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Sorting nexin-3

Definition:

Phosphoinositide-binding protein required for multivesicular body formation. Specifically binds phosphatidylinositol 3-phosphate (PtdIns(P3)). Can also bind phosphatidylinositol 4-phosphate (PtdIns(P4)), phosphatidylinositol 5-phosphate (PtdIns(P5)) and phosphatidylinositol 3,5-biphosphate (PtdIns(3,5)P2) (By similarity). Plays a role in protein transport between cellular compartments. Together with RAB7A facilitates endosome membrane association of the retromer cargo-selective subcomplex (CSC/VPS). May in part act as component of the SNX3-retromer complex which mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. Promotes stability and cell surface expression of epithelial sodium channel (ENAC) subunits SCNN1A and SCNN1G (By similarity). Not involved in EGFR degradation. Involved in the regulation of phagocytosis in dendritic cells possibly by regulating EEA1 recruitment to the nascent phagosomes. Involved in iron homeostasis through regulation of endocytic recycling of the transferrin receptor TFRC presumably by delivering the transferrin:transferrin receptor complex to recycling endosomes; the function may involve the CSC retromer subcomplex (By similarity). In the case of Salmonella enterica infection plays arole in maturation of the Salmonella-containing vacuole (SCV) and promotes recruitment of LAMP1 to SCVs.

References:

[1]. Y Xu, et al. SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P. Nat Cell Biol. 2001 Jul;3(7):658-66. [Content Brief]

[2]. Megan S Harrison, et al. A mechanism for retromer endosomal coat complex assembly with cargo. Proc Natl Acad Sci U S A. 2014 Jan 7;111(1):267-72. [Content Brief]

[3]. Véronique Pons, et al. Hrs and SNX3 functions in sorting and membrane invagination within multivesicular bodies. PLoS Biol. 2008 Sep 2;6(9):e214. [Content Brief]

[4]. Rong Yuan Ray Chua, et al. SNX3 recruits to phagosomes and negatively regulates phagocytosis in dendritic cells. Immunology. 2013 May;139(1):30-47. [Content Brief]

[5]. Ian J McGough, et al. SNX3-retromer requires an evolutionary conserved MON2:DOPEY2:ATP9A complex to mediate Wntless sorting and Wnt secretion. Nat Commun. 2018 Sep 13;9(1):3737. [Content Brief]

[6]. Martin Harterink, et al. A SNX3-dependent retromer pathway mediates retrograde transport of the Wnt sorting receptor Wntless and is required for Wnt secretion. Nat Cell Biol. 2011 Jul 3;13(8):914-923. [Content Brief]

[7]. Virginie Braun, et al. Sorting nexin 3 (SNX3) is a component of a tubular endosomal network induced by Salmonella and involved in maturation of the Salmonella-containing vacuole. Cell Microbiol. 2010 Sep 1;12(9):1352-67. [Content Brief]

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