title: The vesicle trafficking protein Sar1 lowers lipid membrane rigidity.
abstract: The sculpting of membranes into dynamic, curved shapes is central to intracellular cargo trafficking. Though the generation of membrane curvature during trafficking necessarily involves both lipids and membrane-associated proteins, current mechanistic views focus primarily on the formation of rigid cages and curved scaffolds by protein assemblies. Here we report on a different mechanism for the control of membrane deformation, unrelated to the imposition of predefined curvature, involving modulation of membrane material properties: Sar1, a GTPase that regulates vesicle trafficking from the endoplasmic reticulum, lowers the rigidity of the lipid bilayer membrane to which it binds. In vitro assays in which optically trapped microspheres create controlled membrane deformations revealed a monotonic decline in bending modulus as a function of Sar1 concentration, down to nearly zero rigidity, indicating a dramatic lowering of the energetic cost of curvature generation. This is the first demonstration that a vesicle trafficking protein lowers the rigidity of its target membrane, leading to a new conceptual framework for vesicle biogenesis.
authors.affiliation: Department of Biology, University of Oregon, Eugene, Oregon, USA.
authors.forename: Edward I
authors.initials: EI
authors.lastname: Settles
authors.forename: Andrew F
authors.initials: AF
authors.lastname: Loftus
authors.forename: Alesia N
authors.initials: AN
authors.lastname: McKeown
authors.forename: Raghuveer
authors.initials: R
authors.lastname: Parthasarathy
mesh_terms: D001692:Biological Transport; D001696:Biomechanical Phenomena; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D020559:Monomeric GTP-Binding Proteins
references.citation: Semin Cell Dev Biol. 2007 Aug;18(4):424-34
references.pmid: 17686639
references.citation: Phys Rev Lett. 2009 Jan 23;102(3):038102
references.pmid: 19257398
references.citation: J Cell Biol. 2005 Dec 19;171(6):919-24
references.pmid: 16344311
references.citation: Biophys J. 1999 Oct;77(4):1992-2002
references.pmid: 10512819
references.citation: Biophys J. 1995 Jun;68(6):2361-9
references.pmid: 7647240
references.citation: Biophys J. 2007 Sep 15;93(6):2048-55
references.pmid: 17526585
references.citation: Cell. 2007 May 18;129(4):761-72
references.pmid: 17512409
references.citation: Annu Rev Cell Dev Biol. 2004;20:87-123
references.pmid: 15473836
references.citation: J Biol Chem. 1993 Jan 15;268(2):873-9
references.pmid: 8419365
references.citation: Proc Natl Acad Sci U S A. 2008 Aug 19;105(33):11731-6
references.pmid: 18689681
references.citation: Biophys J. 2008 Sep;95(5):2512-9
references.pmid: 18515392
references.citation: Proc Natl Acad Sci U S A. 2009 Apr 7;106(14):5622-6
references.pmid: 19304798
references.citation: Biochim Biophys Acta. 2006 Aug;1761(8):897-912
references.pmid: 16938488
references.citation: Nat Rev Mol Cell Biol. 2006 Oct;7(10):727-38
references.pmid: 16990852
references.citation: Eur Biophys J. 2006 Feb;35(3):281-6
references.pmid: 16211403
references.citation: Nature. 2006 Jan 12;439(7073):234-8
references.pmid: 16407955
references.citation: Cell. 1998 Oct 16;95(2):237-48
references.pmid: 9790530
references.citation: Science. 2009 Mar 6;323(5919):1354-7
references.pmid: 19265022
references.citation: Biochim Biophys Acta. 2009 Jun;1788(6):1387-97
references.pmid: 19248763
references.citation: Biophys J. 1987 Sep;52(3):391-400
references.pmid: 3651558
references.citation: Curr Opin Struct Biol. 2000 Apr;10(2):220-8
references.pmid: 10753805
references.citation: Nature. 2009 May 21;459(7245):379-85
references.pmid: 19458714
references.citation: Biophys Chem. 2008 Sep;137(1):7-12
references.pmid: 18602207
references.citation: Nucleic Acids Res. 2008 Jul 1;36(Web Server issue):W270-5
references.pmid: 18508808
references.citation: Nat Rev Mol Cell Biol. 2006 Jan;7(1):9-19
references.pmid: 16365634
references.citation: Proc Natl Acad Sci U S A. 2009 Sep 8;106(36):15320-5
references.pmid: 19717437
references.citation: Mol Cell Biol. 1999 Mar;19(3):1720-30
references.pmid: 10022859
references.citation: Nat Cell Biol. 2001 Jun;3(6):531-7
references.pmid: 11389436
references.citation: Cell. 2005 Aug 26;122(4):605-17
references.pmid: 16122427
references.citation: Soft Matter. 2006 Dec 13;3(1):24-33
references.pmid: 32680189
references.citation: Biochim Biophys Acta. 2006 Sep;1758(9):1292-302
references.pmid: 16542637
references.citation: Cell. 1998 Apr 17;93(2):263-75
references.pmid: 9568718
references.citation: Science. 2004 Jan 23;303(5657):495-9
references.pmid: 14645856
references.citation: Biophys J. 1996 Sep;71(3):1348-9
references.pmid: 8874009
references.citation: Phys Rev Lett. 2005 Mar 4;94(8):088102
references.pmid: 15783939
references.citation: Biophys J. 2007 Aug 15;93(4):1369-79
references.pmid: 17526591
references.citation: EMBO J. 2005 Jul 6;24(13):2244-53
references.pmid: 15944734
references.citation: Z Naturforsch C. 1973 Nov-Dec;28(11):693-703
references.pmid: 4273690
references.citation: Phys Rev Lett. 2007 Jul 6;99(1):018303
references.pmid: 17678194
references.citation: Proc Natl Acad Sci U S A. 1974 Nov;71(11):4457-61
references.pmid: 4530994
references.citation: Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Apr;65(4 Pt 1):041901
references.pmid: 12005867
references.citation: J Biol Chem. 1997 Dec 5;272(49):30848-51
references.pmid: 9388229
references.citation: Phys Rev Lett. 2002 Jun 10;88(23):238101
references.pmid: 12059401
references.citation: Biophys J. 1995 Mar;68(3):988-96
references.pmid: 7756561
references.citation: Cell. 2008 Mar 7;132(5):807-17
references.pmid: 18329367
references.citation: Nature. 2002 Sep 19;419(6904):271-7
references.pmid: 12239560
references.citation: Nature. 2005 Dec 1;438(7068):590-6
references.pmid: 16319878