The Plant SNX Family and Its Role in Endocytosis

  • Enric Zelazny
  • Rumen Ivanov
  • Thierry Gaude


Separation of functions within the cytoplasm of the eukaryotic cell has resulted in the development of a highly dynamic network of membranous compartments. Among them, the endosomes represent a crossing point for the major cellular trafficking pathways. Indeed, they are responsible for the communication between the cellular compartments, as well as between the cell and its environment, through the regulation of signalling networks and transport of material. The proteins from the sorting nexin (SNX) family have an established role as major regulators of endosomal protein transport in mammals, insects, worms, and yeast. By contrast, research on plant SNXs has been initiated relatively recently. Despite that, the accumulated knowledge suggests that plant SNXs may have evolved different mechanisms of action and might work in a different protein complex environment, compared to their yeast and animal counterparts. In this chapter, we highlight both common and specific characteristics of plant SNX protein function and regulation in comparison to the well-studied mammalian SNX machinery.


Epidermal Growth Factor Receptor Retromer Complex Lytic Vacuole Epidermal Growth Factor Receptor Degradation Vacuolar Sorting Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Bin/Amphiphysin/Rvs domain


Nexin C-terminal domain


Microtubule interacting domain


Forkhead-associated domain


4.1/Ezrin/Radixin/Moesin domain


Kinesin motor domain


PSD95/Dlg1/Zo-1 domain




PHOX homology domain


PHOX associated domain


Rab5-binding domain


Ras-association domain


Regulator of G-protein signalling domain


RhoGAP domain


Src Homology 3 domain


Sorting nexin


S locus receptor kinase


Vacuolar protein sorting


  1. Abas L, Benjamins R, Malenica N, Paciorek T, Wirniewska J, Moulinier-Anzola JC, Sieberer T, Friml J, Luschnig C (2006) Intracellular trafficking and proteolysis of the Arabidopsis auxin-efflux facilitator PIN2 are involved in root gravitropism. Nat Cell Biol 8:249–256PubMedCrossRefGoogle Scholar
  2. Arighi CN, Hartnell LM, Aguilar RC, Haft CR, Bonifacino JS (2004) Role of the mammalian retromer in sorting of the cation-independent mannose 6-phosphate receptor. J Cell Biol 165:123–133PubMedCrossRefGoogle Scholar
  3. Barberon M, Zelazny E, Robert S, Conejero G, Curie C, Friml J, Vert G (2011) Monoubiquitin-dependent endocytosis of the iron-regulated transporter 1 (IRT1) transporter controls iron uptake in plants. Proc Natl Acad Sci U S A 108:E450–E458PubMedCrossRefGoogle Scholar
  4. Bravo J, Karathanassis D, Pacold CM, Pacold ME, Ellson CD, Anderson KE, Butler PJ, Lavenir I, Perisic O, Hawkins PT, Stephens L, Williams RL (2001) The crystal structure of the PX domain from p40(phox) bound to phosphatidylinositol 3-phosphate. Mol Cell 8:829–839PubMedCrossRefGoogle Scholar
  5. Carlton J, Bujny M, Peter BJ, Oorschot VM, Rutherford A, Mellor H, Klumperman J, McMahon HT, Cullen PJ (2004) Sorting nexin-1 mediates tubular endosome-to-TGN transport through coincidence sensing of high-curvature membranes and 3-phosphoinositides. Curr Biol 14:1791–1800PubMedCrossRefGoogle Scholar
  6. Carlton J, Bujny M, Rutherford A, Cullen P (2005a) Sorting nexins–unifying trends and new perspectives. Traffic 6:75–82PubMedCrossRefGoogle Scholar
  7. Carlton JG, Bujny MV, Peter BJ, Oorschot VM, Rutherford A, Arkell RS, Klumperman J, McMahon HT, Cullen PJ (2005b) Sorting nexin-2 is associated with tubular elements of the early endosome, but is not essential for retromer-mediated endosome-to-TGN transport. J Cell Sci 118:4527–4539PubMedCrossRefGoogle Scholar
  8. Cozier GE, Carlton J, McGregor AH, Gleeson PA, Teasdale RD, Mellor H, Cullen PJ (2002) The phox homology (PX) domain-dependent, 3-phosphoinositide-mediated association of sorting nexin-1 with an early sorting endosomal compartment is required for its ability to regulate epidermal growth factor receptor degradation. J Biol Chem 277:48730–48736PubMedCrossRefGoogle Scholar
  9. Cullen PJ (2008) Endosomal sorting and signalling: an emerging role for sorting nexins. Nat Rev Mol Cell Biol 9:574–582PubMedCrossRefGoogle Scholar
  10. Cullen PJ, Korswagen HC (2012) Sorting nexins provide diversity for retromer-dependent trafficking events. Nat Cell Biol 14:29–37CrossRefGoogle Scholar
  11. Dhonukshe P, Tanaka H, Goh T, Ebine K, Mahonen AP, Prasad K, Blilou I, Geldner N, Xu J, Uemura T, Chory J, Ueda T, Nakano A, Scheres B, Friml J (2008) Generation of cell polarity in plants links endocytosis, auxin distribution and cell fate decisions. Nature 456:962–966PubMedCrossRefGoogle Scholar
  12. Dislich B, Than ME, Lichtenthaler SF (2011) Specific amino acids in the BAR domain allow homodimerization and prevent heterodimerization of sorting nexin 33. Biochem J 433:75–83PubMedCrossRefGoogle Scholar
  13. Franch-Marro X, Wendler F, Guidato S, Griffith J, Baena-Lopez A, Itasaki N, Maurice MM, Vincent JP (2008) Wingless secretion requires endosome-to-golgi retrieval of Wntless/Evi/Sprinter by the retromer complex. Nat Cell Biol 10:170–177PubMedCrossRefGoogle Scholar
  14. Frost A, Perera R, Roux A, Spasov K, Destaing O, Egelman EH, De Camilli P, Unger VM (2008) Structural basis of membrane invagination by F-BAR domains. Cell 132:807–817PubMedCrossRefGoogle Scholar
  15. Geldner N, Friml J, Stierhof YD, Jurgens G, Palme K (2001) Auxin transport inhibitors block PIN1 cycling and vesicle trafficking. Nature 413:425–428PubMedCrossRefGoogle Scholar
  16. Geldner N, Hyman DL, Wang X, Schumacher K, Chory J (2007) Endosomal signaling of plant steroid receptor kinase BRI1. Genes Dev 21:1598–1602PubMedCrossRefGoogle Scholar
  17. Gullapalli A, Garrett TA, Paing MM, Griffin CT, Yang Y, Trejo J (2004) A role for sorting nexin 2 in epidermal growth factor receptor down-regulation: evidence for distinct functions of sorting nexin 1 and 2 in protein trafficking. Mol Biol Cell 15:2143–2155PubMedCrossRefGoogle Scholar
  18. Gullapalli A, Wolfe BL, Griffin CT, Magnuson T, Trejo J (2006) An essential role for SNX1 in lysosomal sorting of protease-activated receptor-1: evidence for retromer-, Hrs-, and Tsg101-independent functions of sorting nexins. Mol Biol Cell 17:1228–1238PubMedCrossRefGoogle Scholar
  19. Haberg K, Lundmark R, Carlsson SR (2008) SNX18 is an SNX9 paralog that acts as a membrane tubulator in AP-1-positive endosomal trafficking. J Cell Sci 121:1495–1505PubMedCrossRefGoogle Scholar
  20. Haft CR, de la Luz Sierra M, Barr VA, Haft DH, Taylor SI (1998) Identification of a family of sorting nexin molecules and characterization of their association with receptors. Mol Cell Biol 18:7278–7287PubMedGoogle Scholar
  21. Hettema EH, Lewis MJ, Black MW, Pelham HR (2003) Retromer and the sorting nexins Snx4/41/42 mediate distinct retrieval pathways from yeast endosomes. EMBO J 22:548–557PubMedCrossRefGoogle Scholar
  22. Horazdovsky BF, Davies BA, Seaman MN, McLaughlin SA, Yoon S, Emr SD (1997) A sorting nexin-1 homologue, Vps5p, forms a complex with Vps17p and is required for recycling the vacuolar protein-sorting receptor. Mol Biol Cell 8:1529–1541PubMedGoogle Scholar
  23. Jaillais Y, Fobis-Loisy I, Miege C, Gaude T (2008) Evidence for a sorting endosome in Arabidopsis root cells. Plant J 53:237–247PubMedCrossRefGoogle Scholar
  24. Jaillais Y, Fobis-Loisy I, Miege C, Rollin C, Gaude T (2006) AtSNX1 defines an endosome for auxin-carrier trafficking in Arabidopsis. Nature 443:106–109PubMedCrossRefGoogle Scholar
  25. Jaillais Y, Santambrogio M, Rozier F, Fobis-Loisy I, Miege C, Gaude T (2007) The retromer protein VPS29 links cell polarity and organ initiation in plants. Cell 130:1057–1070PubMedCrossRefGoogle Scholar
  26. Kasai K, Takano J, Miwa K, Toyoda A, Fujiwara T (2011) High boron-induced ubiquitination regulates vacuolar sorting of the BOR1 borate transporter in Arabidopsis thaliana. J Biol Chem 286:6175–6183PubMedCrossRefGoogle Scholar
  27. Kleine-Vehn J, Leitner J, Zwiewka M, Sauer M, Abas L, Luschnig C, Friml J (2008) Differential degradation of PIN2 auxin efflux carrier by retromer-dependent vacuolar targeting. Proc Natl Acad Sci USA 105:17812–17817PubMedCrossRefGoogle Scholar
  28. Koumandou VL, Klute MJ, Herman EK, Nunez-Miguel R, Dacks JB, Field MC (2011) Evolutionary reconstruction of the retromer complex and its function in Trypanosoma brucei. J Cell Sci 124:1496–1509PubMedCrossRefGoogle Scholar
  29. Kurten RC, Cadena DL, Gill GN (1996) Enhanced degradation of EGF receptors by a sorting nexin, SNX1. Science 272:1008–1010PubMedCrossRefGoogle Scholar
  30. Kurten RC, Eddington AD, Chowdhury P, Smith RD, Davidson AD, Shank BB (2001) Self-assembly and binding of a sorting nexin to sorting endosomes. J Cell Sci 114:1743–1756PubMedGoogle Scholar
  31. Larkin MA, Blackshields G, Brown NP, Chenna R, McGettigan PA, McWilliam H, Valentin F, Wallace IM, Wilm A, Lopez R, Thompson JD, Gibson TJ, Higgins DG (2007) Clustal W and clustal X version 2.0. Bioinformatics 23:2947–2948PubMedCrossRefGoogle Scholar
  32. Laxmi A, Pan J, Morsy M, Chen R (2008) Light plays an essential role in intracellular distribution of auxin efflux carrier PIN2 in Arabidopsis thaliana. PLoS One 3:e1510PubMedCrossRefGoogle Scholar
  33. Lundmark R, Carlsson SR (2003) Sorting nexin 9 participates in clathrin-mediated endocytosis through interactions with the core components. J Biol Chem 278:46772–46781PubMedCrossRefGoogle Scholar
  34. Michniewicz M, Zago MK, Abas L, Weijers D, Schweighofer A, Meskiene I, Heisler MG, Ohno C, Zhang J, Huang F, Schwab R, Weigel D, Meyerowitz EM, Luschnig C, Offringa R, Friml J (2007) Antagonistic regulation of PIN phosphorylation by PP2A and PINOID directs auxin flux. Cell 130:1044–1056PubMedCrossRefGoogle Scholar
  35. Niemes S, Labs M, Scheuring D, Krueger F, Langhans M, Jesenofsky B, Robinson DG, Pimpl P (2010a) Sorting of plant vacuolar proteins is initiated in the ER. Plant J 62:601–614PubMedCrossRefGoogle Scholar
  36. Niemes S, Langhans M, Viotti C, Scheuring D, San Wan Yan M, Jiang L, Hillmer S, Robinson DG, Pimpl P (2010b) Retromer recycles vacuolar sorting receptors from the trans-Golgi network. Plant J 61:107–121PubMedCrossRefGoogle Scholar
  37. Nisar S, Kelly E, Cullen PJ, Mundell SJ (2010) Regulation of P2Y1 receptor traffic by sorting Nexin 1 is retromer independent. Traffic 11:508–519PubMedCrossRefGoogle Scholar
  38. Nothwehr SF, Hindes AE (1997) The yeast VPS5/GRD2 gene encodes a sorting nexin-1-like protein required for localizing membrane proteins to the late golgi. J Cell Sci 110(Pt 9):1063–1072PubMedGoogle Scholar
  39. Paciorek T, Zazimalova E, Ruthardt N, Petrasek J, Stierhof YD, Kleine-Vehn J, Morris DA, Emans N, Jurgens G, Geldner N, Friml J (2005) Auxin inhibits endocytosis and promotes its own efflux from cells. Nature 435:1251–1256PubMedCrossRefGoogle Scholar
  40. Perrière G, Gouy M (1996) WWW-query: an on-line retrieval system for biological sequence banks. Biochimie 78:364–369PubMedCrossRefGoogle Scholar
  41. Peter BJ, Kent HM, Mills IG, Vallis Y, Butler PJ, Evans PR, McMahon HT (2004) BAR domains as sensors of membrane curvature: the amphiphysin BAR structure. Science 303:495–499PubMedCrossRefGoogle Scholar
  42. Phan NQ, Kim SJ, Bassham DC (2008) overexpression of Arabidopsis sorting nexin AtSNX2b inhibits endocytic trafficking to the vacuole. Mol Plant 1:961–976PubMedCrossRefGoogle Scholar
  43. Ponting CP (1996) Novel domains in NADPH oxidase subunits, sorting nexins, and PtdIns 3-kinases: binding partners of SH3 domains? Protein Sci 5:2353–2357PubMedCrossRefGoogle Scholar
  44. Pourcher M, Santambrogio M, Thazar N, Thierry AM, Fobis-Loisy I, Miege C, Jaillais Y, Gaude T (2010) Analyses of sorting nexins reveal distinct retromer-subcomplex functions in development and protein sorting in Arabidopsis thaliana. Plant Cell 22:3980–3991PubMedCrossRefGoogle Scholar
  45. Pylypenko O, Lundmark R, Rasmuson E, Carlsson SR, Rak A (2007) The PX-BAR membrane-remodeling unit of sorting nexin 9. EMBO J 26:4788–4800PubMedCrossRefGoogle Scholar
  46. Rahman A, Takahashi M, Shibasaki K, Wu S, Inaba T, Tsurumi S, Baskin TI (2010) Gravitropism of Arabidopsis thaliana roots requires the polarization of PIN2 toward the root tip in meristematic cortical cells. Plant Cell 22:1762–1776PubMedCrossRefGoogle Scholar
  47. Reddy JV, Seaman MN (2001) Vps26p, a component of retromer, directs the interactions of Vps35p in endosome-to-golgi retrieval. Mol Biol Cell 12:3242–3256PubMedGoogle Scholar
  48. Reyes FC, Buono R, Otegui MS (2011) Plant endosomal trafficking pathways. Curr Opin Plant Biol 14:666–673PubMedCrossRefGoogle Scholar
  49. Robinson DG, Pimpl P, Scheuring D, Stierhof YD, Sturm S, Viotti C (2012) Trying to make sense of retromer. Trends Plant Sci 17:431–439PubMedCrossRefGoogle Scholar
  50. Roepstorff K, Grandal MV, Henriksen L, Knudsen SL, Lerdrup M, Grovdal L, Willumsen BM, van Deurs B (2009) Differential effects of EGFR ligands on endocytic sorting of the receptor. Traffic 10:1115–1127PubMedCrossRefGoogle Scholar
  51. Rojas R, Kametaka S, Haft CR, Bonifacino JS (2007) Interchangeable but essential functions of SNX1 and SNX2 in the association of retromer with endosomes and the trafficking of mannose 6-phosphate receptors. Mol Cell Biol 27:1112–1124PubMedCrossRefGoogle Scholar
  52. Seaman MN (2004) Cargo-selective endosomal sorting for retrieval to the Golgi requires retromer. J Cell Biol 165:111–122PubMedCrossRefGoogle Scholar
  53. Seaman MN, Marcusson EG, Cereghino JL, Emr SD (1997) Endosome to Golgi retrieval of the vacuolar protein sorting receptor, Vps10p, requires the function of the VPS29, VPS30, and VPS35 gene products. J Cell Biol 137:79–92PubMedCrossRefGoogle Scholar
  54. Seet LF, Hong W (2006) The phox (PX) domain proteins and membrane traffic. Biochim Biophys Acta 1761:878–896PubMedCrossRefGoogle Scholar
  55. Shibasaki K, Uemura M, Tsurumi S, Rahman A (2009) Auxin response in Arabidopsis under cold stress: underlying molecular mechanisms. Plant Cell 21:3823–3838PubMedCrossRefGoogle Scholar
  56. Shin N, Lee S, Ahn N, Kim SA, Ahn SG, YongPark Z, Chang S (2007) Sorting nexin 9 interacts with dynamin 1 and N-WASP and coordinates synaptic vesicle endocytosis. J Biol Chem 282:28939–28950PubMedCrossRefGoogle Scholar
  57. Soulet F, Yarar D, Leonard M, Schmid SL (2005) SNX9 regulates dynamin assembly and is required for efficient clathrin-mediated endocytosis. Mol Biol Cell 16:2058–2067PubMedCrossRefGoogle Scholar
  58. Stierhof YD, Viotti C, Scheuring D, Sturm S, Robinson DG (2012) Sorting nexins 1 and 2a locate mainly to the TGN. Protoplasma. doi: 10.1007/s00709-012-0399-1 PubMedGoogle Scholar
  59. Strochlic TI, Setty TG, Sitaram A, Burd CG (2007) Grd19/Snx3p functions as a cargo-specific adapter for retromer-dependent endocytic recycling. J Cell Biol 177:115–125PubMedCrossRefGoogle Scholar
  60. Takano J, Tanaka M, Toyoda A, Miwa K, Kasai K, Fuji K, Onouchi H, Naito S, Fujiwara T (2010) Polar localization and degradation of Arabidopsis boron transporters through distinct trafficking pathways. Proc Natl Acad Sci USA 107:5220–5225PubMedCrossRefGoogle Scholar
  61. Teasdale RD, Collins BM (2012) Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease. Biochem J 441:39–59PubMedCrossRefGoogle Scholar
  62. Teasdale RD, Loci D, Houghton F, Karlsson L, Gleeson PA (2001) A large family of endosome-localized proteins related to sorting nexin 1. Biochem J 358:7–16PubMedCrossRefGoogle Scholar
  63. Traer CJ, Rutherford AC, Palmer KJ, Wassmer T, Oakley J, Attar N, Carlton JG, Kremerskothen J, Stephens DJ, Cullen PJ (2007) SNX4 coordinates endosomal sorting of TfnR with dynein-mediated transport into the endocytic recycling compartment. Nat Cell Biol 9:1370–1380PubMedCrossRefGoogle Scholar
  64. van Leeuwen W, Okresz L, Bogre L, Munnik T (2004) Learning the lipid language of plant signalling. Trends Plant Sci 9:378–384PubMedCrossRefGoogle Scholar
  65. van Weering JR, Verkade P, Cullen PJ (2010) SNX-BAR proteins in phosphoinositide-mediated, tubular-based endosomal sorting. Semin Cell Dev Biol 21:371–380PubMedCrossRefGoogle Scholar
  66. van Weering JR, Verkade P, Cullen PJ (2012) SNX-BAR-mediated endosome tubulation is co-ordinated with endosome maturation. Traffic 13:94–107PubMedCrossRefGoogle Scholar
  67. Vanoosthuyse V, Tichtinsky G, Dumas C, Gaude T, Cock JM (2003) Interaction of calmodulin, a sorting nexin and kinase-associated protein phosphatase with the Brassica oleracea S locus receptor kinase. Plant Physiol 133:919–929PubMedCrossRefGoogle Scholar
  68. Voigt B, Timmers AC, Šamaj J, Hlavacka A, Ueda T, Preuss M, Nielsen E, Mathur J, Emans N, Stenmark H, Nakano A, Baluška F, Menzel D (2005) Actin-based motility of endosomes is linked to the polar tip growth of root hairs. Eur J Cell Biol 84:609–621PubMedCrossRefGoogle Scholar
  69. Wang Q, Kaan HY, Hooda RN, Goh SL, Sondermann H (2008) Structure and plasticity of endophilin and sorting nexin 9. Structure 16:1574–1587PubMedCrossRefGoogle Scholar
  70. Wassmer T, Attar N, Harterink M, van Weering JR, Traer CJ, Oakley J, Goud B, Stephens DJ, Verkade P, Korswagen HC, Cullen PJ (2009) The retromer coat complex coordinates endosomal sorting and dynein-mediated transport, with carrier recognition by the trans-Golgi network. Dev Cell 17:110–122PubMedCrossRefGoogle Scholar
  71. Worby CA, Dixon JE (2002) Sorting out the cellular functions of sorting nexins. Nat Rev Mol Cell Biol 3:919–931PubMedCrossRefGoogle Scholar
  72. Xu Y, Hortsman H, Seet L, Wong SH, Hong W (2001) SNX3 regulates endosomal function through its PX-domain-mediated interaction with PtdIns(3)P. Nat Cell Biol 3:658–666PubMedCrossRefGoogle Scholar
  73. Yamazaki M, Shimada T, Takahashi H, Tamura K, Kondo M, Nishimura M, Hara-Nishimura I (2008) Arabidopsis VPS35, a retromer component, is required for vacuolar protein sorting and involved in plant growth and leaf senescence. Plant Cell Physiol 49:142–156PubMedCrossRefGoogle Scholar
  74. Zhong Q, Lazar CS, Tronchere H, Sato T, Meerloo T, Yeo M, Songyang Z, Emr SD, Gill GN (2002) Endosomal localization and function of sorting nexin 1. Proc Natl Acad Sci USA 99:6767–6772PubMedCrossRefGoogle Scholar
  75. Zhong Q, Watson MJ, Lazar CS, Hounslow AM, Waltho JP, Gill GN (2005) Determinants of the endosomal localization of sorting nexin 1. Mol Biol Cell 16:2049–2057PubMedCrossRefGoogle Scholar
  76. Zhou CZ, de La Sierra-Gallay IL, Quevillon-Cheruel S, Collinet B, Minard P, Blondeau K, Henckes G, Aufrere R, Leulliot N, Graille M, Sorel I, Savarin P, de la Torre F, Poupon A, Janin J, van Tilbeurgh H (2003) Crystal structure of the yeast phox homology (PX) domain protein Grd19p complexed to phosphatidylinositol-3-phosphate. J Biol Chem 278:50371–50376PubMedCrossRefGoogle Scholar
  77. Zimmerberg J, McLaughlin S (2004) Membrane curvature: how BAR domains bend bilayers. Curr Biol 14:R250–R252PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  1. 1.Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Unité Mixte de Service 3444 BioSciences Gerland-Lyon SudUniversité Claude Bernard Lyon I, Ecole Normale Supérieure de LyonLyonFrance
  2. 2.Department of Plant BiologySaarland UniversitySaarbrueckenGermany

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