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Vacuolar protein sorting-associated protein 35

Definition:

Acts as component of the retromer cargo-selective complex (CSC). The CSC is believed to be the core functional component of retromer or respective retromer complex variants acting to prevent missorting of selected transmembrane cargo proteins into the lysosomal degradation pathway. The recruitment of the CSC to the endosomal membrane involves RAB7A and SNX3. The CSC seems to associate with the cytoplasmic domain of cargo proteins predominantly via VPS35; however, these interactions seem to be of low affinity and retromer SNX proteins may also contribute to cargo selectivity thus questioning the classical function of the CSC. 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 SNX3-retromer mediates the retrograde endosome-to-TGN transport of WLS distinct from the SNX-BAR retromer pathway. The SNX27-retromer is believed to be involved in endosome-to-plasma membrane trafficking and recycling of a broad spectrum of cargo proteins. The CSC seems to act as recruitment hub for other proteins, such as the WASH complex and TBC1D5 (Probable). Required for retrograde transport of lysosomal enzyme receptor IGF2R and SLC11A2. Required to regulate transcytosis of the polymeric immunoglobulin receptor (pIgR-pIgA). Required for endosomal localization of WASHC2C. Mediates the association of the CSC with the WASH complex via WASHC2. Required for the endosomal localization of TBC1D5.; (Microbial infection) The heterotrimeric retromer cargo-selective complex (CSC) mediates the exit of human papillomavirus from the early endosome and the delivery to the Golgi apparatus.

References:

[1]. Marcel Vergés, et al. The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor. Nat Cell Biol. 2004 Aug;6(8):763-9. [Content Brief]

[2]. David A MacLeod, et al. RAB7L1 interacts with LRRK2 to modify intraneuronal protein sorting and Parkinson's disease risk. Neuron. 2013 Feb 6;77(3):425-39. [Content Brief]

[3]. Kerrie E McNally, et al. Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017 Oct;19(10):1214-1225. [Content Brief]

[4]. Da Jia, et al. Multiple repeat elements within the FAM21 tail link the WASH actin regulatory complex to the retromer. Mol Biol Cell. 2012 Jun;23(12):2352-61. [Content Brief]

[5]. Cecilia N Arighi, et al. Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J Cell Biol. 2004 Apr;165(1):123-33. [Content Brief]

[6]. Eszter Zavodszky, et al. Mutation in VPS35 associated with Parkinson's disease impairs WASH complex association and inhibits autophagy. Nat Commun. 2014 May 13;5:3828. [Content Brief]

[7]. Ian J McGough, et al. Retromer binding to FAM21 and the WASH complex is perturbed by the Parkinson disease-linked VPS35(D620N) mutation. Curr Biol. 2014 Jul 21;24(14):1670-1676. [Content Brief]

[8]. 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]

[9]. Mitsuaki Tabuchi, et al. Retromer-mediated direct sorting is required for proper endosomal recycling of the mammalian iron transporter DMT1. J Cell Sci. 2010 Mar 1;123(Pt 5):756-66. [Content Brief]

[10]. Florian Steinberg, et al. A global analysis of SNX27-retromer assembly and cargo specificity reveals a function in glucose and metal ion transport. Nat Cell Biol. 2013 May;15(5):461-71. [Content Brief]

[11]. Michael E Harbour, et al. Recruitment of the endosomal WASH complex is mediated by the extended 'tail' of Fam21 binding to the retromer protein Vps35. Biochem J. 2012 Feb 15;442(1):209-20. [Content Brief]

[12]. Michael E Harbour, et al. The cargo-selective retromer complex is a recruiting hub for protein complexes that regulate endosomal tubule dynamics. J Cell Sci. 2010 Nov 1;123(Pt 21):3703-17. [Content Brief]

[13]. Andreea Popa, et al. Direct binding of retromer to human papillomavirus type 16 minor capsid protein L2 mediates endosome exit during viral infection. PLoS Pathog. 2015 Feb 18;11(2):e1004699. [Content Brief]

[14]. Pengwei Zhang, et al. Cell-Penetrating Peptide Mediates Intracellular Membrane Passage of Human Papillomavirus L2 Protein to Trigger Retrograde Trafficking. Cell. 2018 Sep 6;174(6):1465-1476.e13. [Content Brief]

[15]. 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]

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