title: SNX27 mediates retromer tubule entry and endosome-to-plasma membrane trafficking of signalling receptors.
abstract: Endocytic sorting of signalling receptors between recycling and degradative pathways is a key cellular process controlling the surface complement of receptors and, accordingly, the cell's ability to respond to specific extracellular stimuli. The β2 adrenergic receptor (β2AR) is a prototypical seven-transmembrane signalling receptor that recycles rapidly and efficiently to the plasma membrane after ligand-induced endocytosis. β2AR recycling is dependent on the receptor's carboxy-terminal PDZ ligand and Rab4. This active sorting process is required for functional resensitization of β2AR-mediated signalling. Here we show that sequence-directed sorting occurs at the level of entry into retromer tubules and that retromer tubules are associated with Rab4. Furthermore, we show that sorting nexin 27 (SNX27) serves as an essential adaptor protein linking β2ARs to the retromer tubule. SNX27 does not seem to directly interact with the retromer core complex, but does interact with the retromer-associated Wiskott-Aldrich syndrome protein and SCAR homologue (WASH) complex. The present results identify a role for retromer in endocytic trafficking of signalling receptors, in regulating a receptor-linked signalling pathway, and in mediating direct endosome-to-plasma membrane traffic.
authors: Department of Psychiatry, University of California at San Francisco, San Francisco, California 94158, USA.
authors: Paul
authors: P
authors: Temkin
authors: Ben
authors: B
authors: Lauffer
authors: Stefanie
authors: S
authors: Jäger
authors: Peter
authors: P
authors: Cimermancic
authors: Nevan J
authors: NJ
authors: Krogan
authors: Mark
authors: M
authors: von Zastrow
references: Traffic. 2007 Jun;8(6):758-73
references: 17488291
references: Curr Opin Cell Biol. 2008 Aug;20(4):427-36
references: 18472259
references: J Cell Sci. 2004 Jul 1;117(Pt 15):3107-17
references: 15190120
references: Dev Cell. 2009 Nov;17(5):699-711
references: 19922874
references: Science. 1996 Aug 9;273(5276):797-801
references: 8670420
references: Nat Cell Biol. 2008 Feb;10(2):170-7
references: 18193037
references: J Cell Biol. 1993 Jun;121(6):1257-69
references: 8509447
references: J Cell Biol. 2007 Apr 9;177(1):115-25
references: 17420293
references: Cell. 2010 Nov 24;143(5):761-73
references: 21111236
references: J Biol Chem. 2006 Feb 3;281(5):2820-7
references: 16316992
references: J Cell Biol. 2004 Apr;165(1):111-22
references: 15078902
references: Annu Rev Pharmacol Toxicol. 2008;48:601-29
references: 17995450
references: J Cell Biol. 2010 Aug 23;190(4):565-74
references: 20733053
references: Proc Natl Acad Sci U S A. 2008 Nov 18;105(46):17812-7
references: 19004783
references: Mol Biol Cell. 2004 Feb;15(2):721-33
references: 14595110
references: J Biol Chem. 2004 Dec 24;279(52):54291-303
references: 15452121
references: Methods. 2011 Jan;53(1):13-9
references: 20708689
references: Annu Rev Pharmacol Toxicol. 2008;48:537-68
references: 18184106
references: Nat Cell Biol. 2004 Aug;6(8):763-9
references: 15247922
references: J Cell Biol. 2000 May 15;149(4):901-14
references: 10811830
references: J Cell Sci. 2007 Jul 15;120(Pt 14):2378-89
references: 17606993
references: J Cell Biol. 2002 Feb 18;156(4):653-64
references: 11839770
references: J Biol Chem. 2004 Sep 3;279(36):37461-9
references: 15192107
references: Mol Pharmacol. 1995 Apr;47(4):666-76
references: 7723728
references: Proc Natl Acad Sci U S A. 1999 Oct 26;96(22):12559-64
references: 10535961
references: J Cell Biol. 2008 Jan 14;180(1):159-72
references: 18195106
references: J Biol Chem. 2009 Aug 14;284(33):22411-22425
references: 19531493
references: J Biol Chem. 1992 Feb 15;267(5):3530-8
references: 1371121
references: Curr Biol. 2004 Oct 26;14(20):1791-800
references: 15498486
references: Mol Pharmacol. 2007 Aug;72(2):429-39
references: 17510209
references: J Cell Sci. 2010 May 1;123(Pt 9):1480-91
references: 20375062
references: J Cell Biol. 2004 Apr;165(1):123-33
references: 15078903
references: Nature. 1999 Sep 16;401(6750):286-90
references: 10499588
references: J Cell Biol. 2008 Nov 3;183(3):513-26
references: 18981234
references: Traffic. 2006 Jun;7(6):663-72
references: 16683916
references: Curr Biol. 2005 Oct 25;15(20):R819-20
references: 16243015
references: J Biol Chem. 2005 Feb 4;280(5):3305-13
references: 15548537
references: J Neurochem. 2006 Feb;96(4):934-49
references: 16412099
references: Nat Rev Mol Cell Biol. 2004 Feb;5(2):121-32
references: 15040445
references: J Biol Chem. 2000 Sep 1;275(35):27221-8
references: 10854436
references: Traffic. 2008 Mar;9(3):380-93
references: 18088323
references: J Cell Sci. 2010 Mar 1;123(Pt 5):756-66
references: 20164305
references: Nat Rev Mol Cell Biol. 2006 Aug;7(8):568-79
references: 16936697
references: J Cell Biol. 1982 Apr;93(1):223-9
references: 6121819