title: Endoplasmic reticulum targeting and insertion of tail-anchored membrane proteins by the GET pathway.
abstract: Hundreds of eukaryotic membrane proteins are anchored to membranes by a single transmembrane domain at their carboxyl terminus. Many of these tail-anchored (TA) proteins are posttranslationally targeted to the endoplasmic reticulum (ER) membrane for insertion by the guided-entry of TA protein insertion (GET) pathway. In recent years, most of the components of this conserved pathway have been biochemically and structurally characterized. Get3 is the pathway-targeting factor that uses nucleotide-linked conformational changes to mediate the delivery of TA proteins between the GET pretargeting machinery in the cytosol and the transmembrane pathway components in the ER. Here we focus on the mechanism of the yeast GET pathway and make a speculative analogy between its membrane insertion step and the ATPase-driven cycle of ABC transporters.
authors.affiliation: Department of Molecular and Cellular Biology, Harvard University, Northwest Laboratories, Cambridge, Massachusetts 02138, USA. vdenic@mcb.harvard.edu
authors.forename: Vladimir
authors.initials: V
authors.lastname: Denic
authors.forename: Volker
authors.initials: V
authors.lastname: Dötsch
authors.forename: Irmgard
authors.initials: I
authors.lastname: Sinning
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000378:metabolism*; D000251:Adenosine Triphosphatases / Q000378:metabolism*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D018390:Gene Targeting / Q000379:methods*; D020662:Guanine Nucleotide Exchange Factors / Q000378:metabolism*; D008565:Membrane Proteins / Q000378:metabolism*; D008954:Models, Biological; D011487:Protein Conformation; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D015398:Signal Transduction / Q000235:genetics*
chemical_list: D018528:ATP-Binding Cassette Transporters; D020662:Guanine Nucleotide Exchange Factors; D008565:Membrane Proteins; D029701:Saccharomyces cerevisiae Proteins; D000251:Adenosine Triphosphatases; C529048:Get3 protein, S cerevisiae
references.citation: Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):14701-6
references.pmid: 14657338
references.citation: Nature. 2007 Nov 29;450(7170):663-9
references.pmid: 18046402
references.citation: J Biol Chem. 2011 Sep 30;286(39):34325-34
references.pmid: 21832041
references.citation: Traffic. 2011 Sep;12(9):1119-23
references.pmid: 21658170
references.citation: Biol Chem. 2009 Aug;390(8):775-82
references.pmid: 19558326
references.citation: Nature. 2011 Aug 24;477(7362):61-6
references.pmid: 21866104
references.citation: PLoS One. 2009 Nov 30;4(11):e8061
references.pmid: 19956640
references.citation: Science. 2011 Aug 5;333(6043):758-62
references.pmid: 21719644
references.citation: J Biol Chem. 2010 Mar 26;285(13):9962-9970
references.pmid: 20106980
references.citation: Mol Cell. 2011 Sep 2;43(5):738-50
references.pmid: 21835666
references.citation: Nat Rev Mol Cell Biol. 2011 Nov 16;12(12):787-98
references.pmid: 22086371
references.citation: Nature. 2011 Jul 10;475(7356):394-7
references.pmid: 21743475
references.citation: Cell. 1998 Jul 24;94(2):181-91
references.pmid: 9695947
references.citation: Nature. 2009 Sep 17;461(7262):361-6
references.pmid: 19675567
references.citation: EMBO J. 2012 Feb 1;31(3):707-19
references.pmid: 22124326
references.citation: Nat Struct Mol Biol. 2011 Mar;18(3):389-91
references.pmid: 21336278
references.citation: Proc Natl Acad Sci U S A. 2010 Jul 6;107(27):12127-32
references.pmid: 20554915
references.citation: FEBS Lett. 2007 Mar 6;581(5):935-8
references.pmid: 17303126
references.citation: Trends Biochem Sci. 2012 Oct;37(10):411-7
references.pmid: 22951232
references.citation: Biol Chem. 2011 Jul;392(7):601-8
references.pmid: 21619481
references.citation: J Mol Biol. 2002 Mar 15;317(1):41-72
references.pmid: 11916378
references.citation: Cell. 2008 Aug 22;134(4):634-45
references.pmid: 18724936
references.citation: Proc Natl Acad Sci U S A. 2012 May 15;109(20):7759-64
references.pmid: 22547793
references.citation: Nature. 2010 May 27;465(7297):507-10
references.pmid: 20364120
references.citation: Genes Cells. 2010 Jan;15(1):29-41
references.pmid: 20015340
references.citation: J Mol Biol. 2012 Sep 21;422(3):366-75
references.pmid: 22684149
references.citation: Mol Cell. 2010 Oct 8;40(1):159-71
references.pmid: 20850366
references.citation: FEBS Lett. 2010 Apr 16;584(8):1509-14
references.pmid: 20206626
references.citation: J Biol Chem. 2012 Mar 9;287(11):8310-7
references.pmid: 22262836
references.citation: Annu Rev Cell Dev Biol. 2011;27:25-56
references.pmid: 21801011
references.citation: Proc Natl Acad Sci U S A. 2009 Dec 15;106(50):21131-6
references.pmid: 19948960
references.citation: Arch Biochem Biophys. 2005 Mar 15;435(2):253-63
references.pmid: 15708368
references.citation: Curr Opin Struct Biol. 2012 Apr;22(2):217-24
references.pmid: 22444563
references.citation: Cell. 2007 Mar 23;128(6):1147-59
references.pmid: 17382883
references.citation: Structure. 2010 Aug 11;18(8):897-902
references.pmid: 20696390
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 1;106(35):14849-54
references.pmid: 19706470