Flipping lipids: why an' what's the reason for?
The biosynthesis of glycoconjugates such as N-glycoproteins and GPI-anchored proteins in eukaryotes and cell wall peptidoglycan and lipopolysaccharide in bacteria requires lipid intermediates to be flipped rapidly across the endoplasmic reticulum or bacterial cytoplasmic membrane (so-called biogenic membranes). Rapid flipping is also required to normalize the number of glycerophospholipids in the two leaflets of the bilayer as the membrane expands in a growing cell. Although lipids diffuse rapidly in the plane of the membrane, the intrinsic rate at which they flip across membranes is very low. Biogenic membranes possess dedicated lipid transporters or flippases to increase flipping to a physiologically sufficient rate. The flippases are "ATP-independent" and facilitate "downhill" transport. Most predicted biogenic membrane flippases have not been identified at the molecular level, and the few flippases that have been identified by genetic approaches have not been biochemically validated. Here we summarize recent progress on this fundamental topic and speculate on the mechanism(s) by which biogenic membrane flippases facilitate transbilayer lipid movement.
Sanyal
Sumana
S
Department of Biochemistry, Weill Cornell Medical College, 1300 York Avenue, New York, New York 10065, USA.
Menon
Anant K
AK
D000818:Animals; D001692:Biological Transport; D002462:Cell Membrane / Q000378:metabolism; D002473:Cell Wall / Q000378:metabolism; D050356:Lipid Metabolism; D008055:Lipids / Q000737:chemistry*
D008055:Lipids
J Bacteriol. 2008 Nov;190(21):7298-301
18708495
Proc Natl Acad Sci U S A. 2009 May 26;106(21):8555-60
19433801
Mol Microbiol. 1998 Mar;27(6):1171-82
9570402
Biochemistry. 2008 Jul 29;47(30):7937-46
18597486
J Biol Chem. 1989 Jan 25;264(3):1584-93
2521484
Proc Natl Acad Sci U S A. 1979 Dec;76(12):6245-9
118463
Methods Enzymol. 1983;96:xxix-lv
6656627
Biochim Biophys Acta. 2008 Jul-Aug;1778(7-8):1591-600
18439418
Nature. 1987 May 28-Jun 3;327(6120):341-3
3587349
FEMS Microbiol Rev. 2008 Mar;32(2):208-33
18081839
Prostaglandins Leukot Essent Fatty Acids. 2008 Sep-Nov;79(3-5):117-21
19008088
J Phys Chem B. 2009 May 14;113(19):6745-8
19385639
J Bacteriol. 2006 Jul;188(14):5124-35
16816184
Nature. 1977 Nov 17;270(5634):268-9
201859
J Biol Chem. 1999 Dec 3;274(49):35129-38
10574995
Biochemistry. 2004 Mar 16;43(10):2673-81
15005602
Eukaryot Cell. 2007 Sep;6(9):1625-34
17616631
Biophys J. 2000 May;78(5):2628-40
10777759
Nat Rev Microbiol. 2009 Sep;7(9):677-83
19633680
J Biol Chem. 2002 Jul 12;277(28):25337-43
12000768
FEMS Microbiol Lett. 2008 Oct;287(1):76-84
18707624
Mol Microbiol. 2006 May;60(3):542-52
16629659
Mol Biol Cell. 2001 Feb;12(2):487-501
11179430
Traffic. 2000 Aug;1(8):605-13
11208148
Biol Chem. 2002 Sep;383(9):1435-40
12437136
Biochemistry. 2003 Jan 14;42(1):231-7
12515559
J Biol Chem. 2007 Dec 7;282(49):36077-89
17928292
Chembiochem. 2000 Aug 18;1(2):86-102
11828402
Biochemistry. 2004 Aug 24;43(33):10710-8
15311932
J Bacteriol. 2000 Aug;182(15):4198-206
10894727
Biochemistry. 1971 Mar 30;10(7):1111-20
4324203
Biochemistry. 1994 May 31;33(21):6721-31
8204607
Mol Cell. 2008 Feb 1;29(2):191-206
18243114
J Biol Chem. 2003 May 9;278(19):16534-42
12621029
J Biol Chem. 1998 May 15;273(20):12466-75
9575204
Glycobiology. 2001 May;11(5):61R-70R
11425794
Biochemistry. 1987 Nov 17;26(23):7205-10
3322396
J Bacteriol. 1985 Jul;163(1):208-12
3891726
J Phys Chem B. 2007 Dec 6;111(48):13554-9
17988118
J Cell Biol. 2000 Jul 10;150(1):77-88
10893258
Science. 2005 Dec 2;310(5753):1461-5
16322449
J Bacteriol. 1996 Apr;178(7):2102-7
8606190
J Biol Chem. 2008 Feb 15;283(7):4087-93
18077451
J Bacteriol. 2009 Oct;191(19):6020-8
19666716
Biochim Biophys Acta. 1998 Nov 10;1376(3):391-400
9804997
Curr Biol. 2000 Mar 9;10(5):241-52
10712902
J Membr Biol. 1992 Jan;125(2):97-8
1552565
J Biol Chem. 2005 Mar 25;280(12):12028-34
15661733
Biochemistry. 2004 Jun 15;43(23):7643-52
15182207
Mol Microbiol. 2007 May;64(4):1105-14
17501931
J Biol Chem. 2003 Jul 4;278(27):24586-93
12714595
J Biol Chem. 1993 Jun 25;268(18):13110-7
8514752
Biochemistry. 2001 Sep 4;40(35):10500-6
11523991
Curr Opin Struct Biol. 2004 Aug;14(4):405-12
15313233
J Lipid Res. 1981 Mar;22(3):391-403
7017050
J Biol Chem. 2009 Jul 24;284(30):19835-42
19494107
Proc Natl Acad Sci U S A. 1974 Nov;71(11):4457-61
4530994
Biophys J. 2005 Oct;89(4):2522-32
16085770
Proc Natl Acad Sci U S A. 2008 Oct 7;105(40):15553-7
18832143
J Biol Chem. 1993 Aug 5;268(22):16746-53
8344954
Biochim Biophys Acta. 2008 Jun;1780(6):861-8
18387370
J Cell Biol. 1995 Aug;130(3):529-36
7622555
J Biol Chem. 2007 Jan 12;282(2):821-5
17130120
Proc Natl Acad Sci U S A. 1977 May;74(5):1821-5
405668
Annu Rev Microbiol. 2003;57:203-24
14527277
Proc Natl Acad Sci U S A. 1982 Mar;79(5):1520-4
6951194
Biochemistry. 1997 Apr 22;36(16):4969-78
9125519
Nature. 2002 Jan 24;415(6870):447-50
11807558
Curr Opin Chem Biol. 2007 Dec;11(6):654-61
17981493
Biochemistry. 1990 Feb 27;29(8):2023-7
2328236
Chem Commun (Camb). 2005 Jan 28;(4):453-5
15654367
Biochemistry. 2002 Apr 30;41(17):5605-12
11969421
Cell Mol Life Sci. 2006 Dec;63(24):2908-21
17103115
Biochim Biophys Acta. 2000 Mar 10;1469(1):43-61
10692637
Microbiol Mol Biol Rev. 2007 Dec;71(4):620-35
18063720
Glycobiology. 1998 Dec;8(12):1195-205
9858641
Curr Protein Pept Sci. 2005 Oct;6(5):399-411
16248792
Nature. 2008 Jul 31;454(7204):E3-4; discussion E4-5
18668045
J Biol Chem. 1996 Mar 22;271(12):6651-7
8636082
J Am Chem Soc. 2006 Sep 27;128(38):12462-7
16984196
Proc Natl Acad Sci U S A. 2009 Jan 20;106(3):767-72
19129492
Org Biomol Chem. 2005 Apr 7;3(7):1275-83
15785818
J Lipid Res. 2007 May;48(5):993-1011
17361015
Trends Cell Biol. 2004 Dec;14(12):670-7
15564043
Nat Rev Drug Discov. 2006 Apr;5(4):321-32
16531990
Cell. 1985 Aug;42(1):51-60
3893747
Annu Rev Biochem. 1987;56:63-87
3304145
Annu Rev Biophys. 2008;37:23-42
18573071
Microbiology (Reading). 2004 Dec;150(Pt 12):4095-105
15583162