title: Receptor-mediated transport of vacuolar proteins: a critical analysis and a new model.
abstract: In this article we challenge the widely accepted view that receptors for soluble vacuolar proteins (VSRs) bind to their ligands at the trans-Golgi network (TGN) and transport this cargo via clathrin-coated vesicles (CCV) to a multivesicular prevacuolar compartment. This notion, which we term the "classical model" for vacuolar protein sorting, further assumes that low pH in the prevacuolar compartment causes VSR-ligand dissociation, resulting in a retromer-mediated retrieval of the VSRs to the TGN. We have carefully evaluated the literature with respect to morphology and function of the compartments involved, localization of key components of the sorting machinery, and conclude that there is little direct evidence in its favour. Firstly, unlike mammalian cells where the sorting receptor for lysosomal hydrolases recognizes its ligand in the TGN, the available data suggests that in plants VSRs interact with vacuolar cargo ligands already in the endoplasmic reticulum. Secondly, the evidence supporting the packaging of VSR-ligand complexes into CCV at the TGN is not conclusive. Thirdly, the prevacuolar compartment appears to have a pH unsuitable for VSR-ligand dissociation and lacks the retromer core and the sorting nexins needed for VSR recycling. We present an alternative model for protein sorting in the TGN that draws attention to the much overlooked role of Ca(2+) in VSR-ligand interactions and which may possibly also be a factor in the sequestration of secretory proteins.
authors.affiliation: Centre for Organismal Studies (COS), University of Heidelberg, Heidelberg, Germany.
authors.forename: David G
authors.initials: DG
authors.lastname: Robinson
authors.forename: Peter
authors.initials: P
authors.lastname: Pimpl
mesh_terms: D001692:Biological Transport; D002451:Cell Compartmentation; D008954:Models, Biological; D010940:Plant Proteins / Q000378:metabolism*; D011485:Protein Binding; D014617:Vacuoles / Q000378:metabolism*; D033921:Vesicular Transport Proteins / Q000378:metabolism*
chemical_list: D010940:Plant Proteins; D033921:Vesicular Transport Proteins
references.citation: J Cell Biol. 1997 Nov 3;139(3):601-11
references.pmid: 9348278
references.citation: J Biol Chem. 2013 Mar 29;288(13):8815-25
references.pmid: 23362252
references.citation: Plant Physiol. 2000 Dec;124(4):1814-27
references.pmid: 11115896
references.citation: Plant J. 2004 Mar;37(5):678-93
references.pmid: 14871308
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):16095-100
references.pmid: 14657332
references.citation: J Cell Biol. 1996 Apr;133(2):257-68
references.pmid: 8609160
references.citation: Plant Cell. 2002 May;14(5):1077-92
references.pmid: 12034898
references.citation: Plant Cell. 2009 Apr;21(4):1212-29
references.pmid: 19376937
references.citation: Plant Physiol. 2003 Jun;132(2):618-28
references.pmid: 12805592
references.citation: Plant Physiol. 2004 Mar;134(3):898-908
references.pmid: 15020753
references.citation: Plant Cell. 2010 Dec;22(12):3980-91
references.pmid: 21156856
references.citation: Nature. 2006 Sep 7;443(7107):106-9
references.pmid: 16936718
references.citation: Mol Cell Biol. 2007 Feb;27(3):1112-24
references.pmid: 17101778
references.citation: Plant Biol (Stuttg). 2011 May;13(3):421-30
references.pmid: 21489092
references.citation: Small GTPases. 2012 Jan-Mar;3(1):23-7
references.pmid: 22710734
references.citation: J Cell Sci. 2012 Aug 1;125(Pt 15):3511-8
references.pmid: 22935651
references.citation: Plant J. 1993 Nov;4(5):793-800
references.pmid: 8275099
references.citation: Traffic. 2007 Oct;8(10):1452-64
references.pmid: 17696967
references.citation: Nature. 1987 Apr 23-29;326(6115):760-5
references.pmid: 3494949
references.citation: Protoplasma. 2013 Jun;250(3):671-81
references.pmid: 23053766
references.citation: Nature. 1997 Aug 14;388(6643):691-3
references.pmid: 9262405
references.citation: Plant Cell. 2013 Feb;25(2):499-516
references.pmid: 23424247
references.citation: Plant Cell. 2013 Jun;25(6):2217-35
references.pmid: 23771894
references.citation: Plant Cell. 2012 Dec;24(12):4776
references.pmid: 23275576
references.citation: Plant Cell Physiol. 1997 Dec;38(12):1414-20
references.pmid: 9522472
references.citation: Plant Cell. 2005 Mar;17(3):888-902
references.pmid: 15722471
references.citation: Plant Physiol. 2013 Aug;162(4):1897-910
references.pmid: 23766365
references.citation: Proc Natl Acad Sci U S A. 1998 Aug 18;95(17):9920-5
references.pmid: 9707576
references.citation: Dev Cell. 2011 May 17;20(5):652-62
references.pmid: 21571222
references.citation: Protoplasma. 2001;215(1-4):64-76
references.pmid: 11732066
references.citation: J Biol Chem. 1993 Apr 5;268(10):7465-8
references.pmid: 8385108
references.citation: Mol Biol Cell. 2003 Jan;14(1):142-55
references.pmid: 12529433
references.citation: Plant Cell. 2011 Sep;23(9):3463-81
references.pmid: 21934143
references.citation: J Biol Chem. 2002 Mar 8;277(10):8708-15
references.pmid: 11748226
references.citation: Plant J. 2006 Apr;46(1):95-110
references.pmid: 16553898
references.citation: Traffic. 2011 Aug;12(8):963-71
references.pmid: 21463457
references.citation: Curr Biol. 2007 Mar 20;17(6):520-7
references.pmid: 17306539
references.citation: Trends Plant Sci. 2014 Mar;19(3):134-9
references.pmid: 24263003
references.citation: Plant Cell. 2011 Jan;23(1):240-57
references.pmid: 21258004
references.citation: Plant Physiol. 2008 Aug;147(4):1516-26
references.pmid: 18678743
references.citation: Curr Opin Cell Biol. 2008 Feb;20(1):4-11
references.pmid: 18222686
references.citation: Proc Natl Acad Sci U S A. 2013 Jun 18;110(25):10318-23
references.pmid: 23733933
references.citation: Plant Cell Physiol. 2004 Jan;45(1):9-17
references.pmid: 14749481
references.citation: Mol Biol Cell. 2012 Jun;23(12):2327-38
references.pmid: 22553351
references.citation: Nat Cell Biol. 2011 Dec 22;14(1):29-37
references.pmid: 22193161
references.citation: Plant J. 2009 Jul;59(1):169-78
references.pmid: 19309456
references.citation: Plant J. 2010 May 1;62(4):601-14
references.pmid: 20149141
references.citation: Cell. 1994 Mar 11;76(5):841-52
references.pmid: 8124720
references.citation: J Cell Biol. 1993 Jun;121(5):997-1010
references.pmid: 8099077
references.citation: Mol Biol Cell. 1997 Aug;8(8):1529-41
references.pmid: 9285823
references.citation: Plant Cell. 2006 Mar;18(3):715-30
references.pmid: 16461582
references.citation: Traffic. 2008 Sep;9(10):1599-612
references.pmid: 18627574
references.citation: Plant Cell Physiol. 2013 Jun;54(6):838-47
references.pmid: 23543752
references.citation: Plant Cell. 2012 May;24(5):1714-32
references.pmid: 22570446
references.citation: Plant Cell. 2012 Dec;24(12):5058-73
references.pmid: 23263768
references.citation: Plant Cell. 1998 May;10(5):825-36
references.pmid: 9596640
references.citation: Plant Cell. 2009 Aug;21(8):2341-56
references.pmid: 19654264
references.citation: Plant J. 2009 Dec;60(5):865-81
references.pmid: 19709389
references.citation: Plant Cell. 2010 Aug;22(8):2825-37
references.pmid: 20807880
references.citation: Plant Physiol. 2004 Nov;136(3):3435-9
references.pmid: 15542497
references.citation: Plant Physiol. 2010 Sep;154(1):134-48
references.pmid: 20625000
references.citation: Plant Cell. 2010 Apr;22(4):1344-57
references.pmid: 20435907
references.citation: J Cell Biol. 2009 Dec 28;187(7):1055-69
references.pmid: 20026655
references.citation: Traffic. 2005 Aug;6(8):615-25
references.pmid: 15998318
references.citation: Plant Physiol. 2008 Aug;147(4):1675-89
references.pmid: 18567829
references.citation: J Cell Biol. 1994 Dec;127(6 Pt 1):1557-74
references.pmid: 7798312
references.citation: Plant Cell. 1992 Mar;4(3):307-18
references.pmid: 1498598
references.citation: Cell. 1992 Jan 24;68(2):353-64
references.pmid: 1310258
references.citation: Plant Physiol. 1999 Apr;119(4):1165-76
references.pmid: 10198075
references.citation: Biochim Biophys Acta. 1999 Nov 16;1435(1-2):61-70
references.pmid: 10561538
references.citation: Plant Cell. 2009 Mar;21(3):749-66
references.pmid: 19304934
references.citation: Plant Cell Physiol. 2002 Jul;43(7):726-42
references.pmid: 12154135
references.citation: Plant J. 2010 Nov;64(4):577-88
references.pmid: 20807215
references.citation: Plant Cell. 2011 May;23(5):1920-31
references.pmid: 21551390
references.citation: FEBS Lett. 2002 Mar 13;514(2-3):355-60
references.pmid: 11943181
references.citation: Plant Cell. 2006 Jun;18(6):1477-97
references.pmid: 16714388
references.citation: Cell. 1988 Feb 12;52(3):329-41
references.pmid: 2964276
references.citation: Mol Plant. 2011 Sep;4(5):845-53
references.pmid: 21430175
references.citation: Plant Cell. 2004 Mar;16(3):672-93
references.pmid: 14973159
references.citation: J Exp Bot. 2011 May;62(8):2949-57
references.pmid: 21357769
references.citation: J Control Release. 2002 Jul 18;82(1):71-82
references.pmid: 12106978
references.citation: Plant Mol Biol. 1998 Sep;38(1-2):127-44
references.pmid: 9738964
references.citation: Protoplasma. 2013 Feb;250(1):235-40
references.pmid: 22447127
references.citation: Plant Physiol. 2008 Aug;147(4):1565-74
references.pmid: 18678748
references.citation: Traffic. 2011 Mar;12(3):313-29
references.pmid: 21134079
references.citation: EMBO J. 2010 Aug 18;29(16):2700-14
references.pmid: 20717140
references.citation: J Cell Biol. 1998 Mar 9;140(5):1023-37
references.pmid: 9490717
references.citation: Cell. 2005 Sep 9;122(5):735-49
references.pmid: 16143105
references.citation: Plant Physiol. 2008 Jan;146(1):116-28
references.pmid: 18024560
references.citation: Plant Cell. 2010 Dec;22(12):3992-4008
references.pmid: 21177482
references.citation: Plant Physiol. 1999 Oct;121(2):333-44
references.pmid: 10517824
references.citation: J Cell Sci. 2009 Jul 15;122(Pt 14):2371-82
references.pmid: 19531583
references.citation: Protoplasma. 2007;230(1-2):1-11
references.pmid: 17351731
references.citation: J Cell Biol. 2012 Dec 24;199(7):1057-66
references.pmid: 23266954
references.citation: Nat Chem Biol. 2012 May 06;8(6):583-9
references.pmid: 22561410
references.citation: Plant Physiol. 1997 Sep;115(1):29-39
references.pmid: 9306690
references.citation: Plant J. 2010 Jan;61(1):107-21
references.pmid: 19796370
references.citation: Trends Plant Sci. 2012 Jul;17(7):431-9
references.pmid: 22502774
references.citation: Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32
references.pmid: 15040445
references.citation: Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3403-7
references.pmid: 8159760
references.citation: Annu Rev Biochem. 1987;56:829-52
references.pmid: 3304148
references.citation: J Electron Microsc Tech. 1991 Jan;17(1):2-14
references.pmid: 1993935
references.citation: Plant Cell. 2006 May;18(5):1239-52
references.pmid: 16582012
references.citation: Plant Cell Physiol. 2006 Sep;47(9):1187-94
references.pmid: 16926167
references.citation: Curr Opin Plant Biol. 2011 Dec;14(6):674-82
references.pmid: 21945181
references.citation: FEBS Lett. 2012 Sep 21;586(19):3293-8
references.pmid: 22796492
references.citation: J Biol Chem. 2008 Apr 11;283(15):10124-34
references.pmid: 18272523
references.citation: Nat Cell Biol. 2000 Jun;2(6):376-8
references.pmid: 10854330
references.citation: Trends Cell Biol. 2013 Jun;23(6):279-88
references.pmid: 23414967
references.citation: Annu Rev Cell Dev Biol. 2012;28:309-36
references.pmid: 22831640
references.citation: J Biol Chem. 1998 Oct 2;273(40):25915-21
references.pmid: 9748267
references.citation: Plant Cell. 2005 Jan;17(1):132-48
references.pmid: 15632053
references.citation: Semin Cell Dev Biol. 2010 Jun;21(4):371-80
references.pmid: 19914387
references.citation: J Exp Bot. 2012 Feb;63(4):1525-42
references.pmid: 22200666
references.citation: Plant Cell Physiol. 2008 Feb;49(2):142-56
references.pmid: 18222962
references.citation: Plant Cell Physiol. 2002 Oct;43(10):1086-95
references.pmid: 12407187
references.citation: Plant Physiol. 2013 Jan;161(1):121-33
references.pmid: 23175753
references.citation: Plant J. 2011 Jan;65(2):309-18
references.pmid: 21223394
references.citation: PLoS One. 2010 Jun 28;5(6):e11342
references.pmid: 20596537
references.citation: Mol Plant. 2013 Sep;6(5):1419-37
references.pmid: 23702593
references.citation: Trends Cell Biol. 2005 Feb;15(2):68-75
references.pmid: 15695093
references.citation: Nature. 2007 Oct 25;449(7165):1063-7
references.pmid: 17891154
references.citation: Nature. 2007 Jul 26;448(7152):488-92
references.pmid: 17653190