title: Protein-phospholipid interactions in nonclassical protein secretion: problem and methods of study.
abstract: Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 and 2, are exported as a result of their direct translocation through the cell membrane. This process requires specific interactions of released proteins with membrane phospholipids. In this review written by a cell biologist, a structural biologist and two membrane engineers, we discuss the following subjects: (i) Phenomenon of nonclassical protein release and its biological significance; (ii) Composition of the FGF1 multiprotein release complex (MRC); (iii) The relationship between FGF1 export and acidic phospholipid externalization; (iv) Interactions of FGF1 MRC components with acidic phospholipids; (v) Methods to study the transmembrane translocation of proteins;  (vi) Membrane models to study nonclassical protein release.
authors: Maine Medical Center Research Institute, 81 Research Drive, Scarborough, ME 04074, USA. prudoi@mmc.org.
authors: Igor
authors: I
authors: Prudovsky
authors: Thallapuranam Krishnaswamy Suresh
authors: TK
authors: Kumar
authors: Sarah
authors: S
authors: Sterling
authors: David
authors: D
authors: Neivandt
references: Langmuir. 2004 Aug 17;20(17):7232-9
references: 15301510
references: Biochemistry. 2009 Nov 3;48(43):10220-34
references: 19746969
references: Biochem Biophys Res Commun. 2003 Oct 31;310(4):1041-7
references: 14559220
references: J Cell Biol. 2010 Feb 22;188(4):527-36
references: 20156967
references: Langmuir. 2010 Jun 15;26(12):9710-9
references: 20394443
references: Langmuir. 2007 Jun 19;23(13):7155-61
references: 17523684
references: J Biochem Biophys Methods. 1999 Jul 28;40(1-2):27-37
references: 10481949
references: Nat Rev Mol Cell Biol. 2009 Feb;10(2):148-55
references: 19122676
references: Phys Rev Lett. 2009 Jun 5;102(22):228102
references: 19658904
references: J Cell Physiol. 1995 Mar;162(3):388-99
references: 7860646
references: J Biol Chem. 2004 Feb 20;279(8):6244-51
references: 14645213
references: Surf Sci Rep. 2006 Nov 15;61(10):429-444
references: 32287559
references: J Biol Chem. 2011 Sep 30;286(39):34382-90
references: 21816817
references: J Cell Physiol. 1992 Apr;151(1):81-93
references: 1560052
references: Langmuir. 2011 Jun 21;27(12):7760-7
references: 21595453
references: J Biol Chem. 2001 Feb 16;276(7):5147-51
references: 11087725
references: Langmuir. 2010 Dec 7;26(23):18266-72
references: 20977244
references: Chem Phys Lipids. 2010 Feb;163(2):200-6
references: 19931234
references: J Cell Sci. 2002 Sep 15;115(Pt 18):3619-31
references: 12186948
references: Biochim Biophys Acta. 2008 Oct;1778(10):2368-77
references: 18590699
references: J Cell Sci. 2004 Apr 1;117(Pt 9):1727-36
references: 15075234
references: Langmuir. 2004 Oct 12;20(21):8961-5
references: 15461473
references: Biochemistry. 1997 Nov 18;36(46):14146-58
references: 9369487
references: Biopolymers. 2000;57(2):117-25
references: 10766962
references: J Am Chem Soc. 2007 Sep 12;129(36):11079-84
references: 17696532
references: J Cell Physiol. 2011 Nov;226(11):3064-75
references: 21302306
references: J Am Chem Soc. 2010 Aug 11;132(31):10656-7
references: 20681689
references: Biophys J. 2005 Sep;89(3):1780-8
references: 16127170
references: Front Biosci. 2002 May 01;7:d1356-68
references: 11991838
references: Biophys J. 2010 Sep 8;99(5):1397-407
references: 20816051
references: Biochem J. 2006 Jun 1;396(2):201-14
references: 16683912
references: PLoS One. 2012;7(5):e36485
references: 22606265
references: Biophys J. 2007 Aug 1;93(3):866-75
references: 17483186
references: Langmuir. 2006 Oct 24;22(22):9096-9
references: 17042516
references: Langmuir. 2006 Sep 26;22(20):8333-6
references: 16981745
references: FEBS Lett. 2004 Sep 10;574(1-3):55-61
references: 15358539
references: Biophys J. 1992 Dec;63(6):1667-71
references: 19431869
references: J Phys Chem B. 2010 Feb 11;114(5):1903-14
references: 20073520
references: J Phys Chem B. 2010 Jul 29;114(29):9485-95
references: 20614879
references: Biochemistry. 2005 Nov 29;44(47):15472-9
references: 16300395
references: J Pept Sci. 2008 Apr;14(4):503-9
references: 17994618
references: J Biol Chem. 1998 Aug 28;273(35):22217-23
references: 9712835
references: J Am Chem Soc. 2010 Jun 16;132(23):8037-47
references: 20486664
references: Cancer Res. 2006 May 1;66(9):4795-801
references: 16651434
references: Crit Rev Clin Lab Sci. 2008;45(1):91-135
references: 18293181
references: Methods. 2008 Oct;46(2):116-22
references: 18634881
references: J Phys Chem B. 2008 May 22;112(20):6373-8
references: 18426235
references: J Biol Chem. 1998 Aug 28;273(35):22224-31
references: 9712836
references: Biochim Biophys Acta. 2006 Sep;1758(9):1257-73
references: 16524559
references: Langmuir. 2005 Oct 11;21(21):9644-50
references: 16207048
references: Chemphyschem. 2008 Apr 4;9(5):721-8
references: 18338419
references: J Biol Chem. 2001 Jun 29;276(26):23769-76
references: 11306575
references: Langmuir. 2004 Nov 23;20(24):10567-75
references: 15544386
references: J Am Chem Soc. 2007 Feb 21;129(7):2094-100
references: 17263532
references: J Biol Chem. 2004 Oct 15;279(42):43411-8
references: 15302870
references: J Biol Chem. 1994 Aug 19;269(33):21191-7
references: 8063740
references: Biochemistry. 2007 Aug 14;46(32):9225-38
references: 17636870
references: Am J Clin Nutr. 2008 Sep;88(3):826S-9S
references: 18779302
references: Cell Mol Life Sci. 2009 Jan;66(2):225-35
references: 18850066
references: Proc Natl Acad Sci U S A. 1999 Jul 20;96(15):8461-6
references: 10411897
references: Chembiochem. 2000 Aug 18;1(2):86-102
references: 11828402
references: Biophys J. 2009 Aug 5;97(3):L01-3
references: 19651025
references: J Am Chem Soc. 2004 Dec 15;126(49):16267-74
references: 15584764
references: Phys Rev Lett. 2003 Mar 28;90(12):128101
references: 12688904
references: Biophys J. 2005 Aug;89(2):1081-93
references: 15879469
references: J Phys Chem B. 2009 May 28;113(21):7491-7
references: 19415915
references: Cytometry. 1999 Jul 1;36(3):176-82
references: 10404965
references: Semin Cell Dev Biol. 2001 Apr;12(2):139-48
references: 11292380
references: Adv Colloid Interface Sci. 2006 Sep 13;121(1-3):51-75
references: 16769012
references: Mol Biol Cell. 2008 Nov;19(11):4863-74
references: 18784255
references: Biochemistry. 1996 Nov 26;35(47):14773-81
references: 8942639
references: Annu Rev Biophys Biomol Struct. 2007;36:151-69
references: 17477838
references: Langmuir. 2010 Oct 19;26(20):16055-62
references: 20873825
references: EMBO J. 1990 May;9(5):1503-10
references: 2328723
references: Eur J Biochem. 1997 Jun 1;246(2):328-35
references: 9208921
references: J Biol Chem. 1995 Dec 8;270(49):29039-42
references: 7493920
references: Langmuir. 2007 Aug 14;23(17):8925-31
references: 17629307
references: Phys Rev B Condens Matter. 1987 Feb 15;35(6):3047-3050
references: 9941799
references: Langmuir. 2010 May 4;26(9):6140-4
references: 20387820
references: Proc Natl Acad Sci U S A. 1992 Nov 15;89(22):10691-5
references: 1279690
references: EMBO J. 1992 Dec;11(13):4835-42
references: 1281450
references: Langmuir. 2006 Oct 24;22(22):9339-44
references: 17042551
references: Biophys J. 2006 Sep 1;91(5):1832-43
references: 16766622
references: J Cell Sci. 2003 Jun 15;116(Pt 12):2399-408
references: 12724354
references: Langmuir. 2007 Jan 16;23(2):589-97
references: 17209610
references: J Am Chem Soc. 2011 Jun 15;133(23):8794-7
references: 21595482
references: J Biol Chem. 2003 May 2;278(18):16405-13
references: 12598523
references: J Fluoresc. 2006 Sep;16(5):671-8
references: 17013676
references: Anal Bioanal Chem. 2011 Apr;399(10):3547-54
references: 21293959
references: Nat Neurosci. 2011 Dec 25;15(2):243-9
references: 22197832
references: J Cell Sci. 1997 May;110 ( Pt 10):1169-78
references: 9191041
references: J Am Chem Soc. 2010 Oct 27;132(42):14971-8
references: 20882964
references: Biophys J. 1994 Jul;67(1):217-26
references: 7918990
references: Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15479-84
references: 17030799
references: J Biol Chem. 2001 Jul 6;276(27):25549-57
references: 11432880
references: Vascul Pharmacol. 2011 Mar-Jun;54(3-6):59-67
references: 21440088
references: J Am Chem Soc. 2007 Feb 7;129(5):1420-7
references: 17263427
references: J Biol Inorg Chem. 2008 Feb;13(2):195-205
references: 17957393
references: Biochemistry. 1995 Aug 8;34(31):9913-20
references: 7543282
references: J Cell Biol. 2002 Jul 22;158(2):201-8
references: 12135982
references: Biochim Biophys Acta. 2010 Feb;1798(2):297-302
references: 19835837
references: J Struct Biol. 2009 Oct;168(1):37-52
references: 19508895
references: Biochemistry. 2000 Dec 12;39(49):15091-100
references: 11106487
references: Biochemistry. 1993 Jun 29;32(25):6419-26
references: 7686045
references: J Cell Sci. 2003 Jul 1;116(Pt 13):2687-96
references: 12746488
references: Tumour Biol. 2004 Jan-Apr;25(1-2):31-40
references: 15192310
references: Eur J Neurosci. 2004 Jan;19(1):55-64
references: 14750963
references: Langmuir. 2005 Aug 2;21(16):7476-82
references: 16042482
references: J Am Chem Soc. 2009 Feb 4;131(4):1401-3
references: 19140762
references: Anal Chem. 2011 Feb 15;83(4):1342-9
references: 21229969
references: Biochemistry. 2005 Nov 8;44(44):14431-42
references: 16262243
references: Vib Spectrosc. 2009 May 26;50(1):106-115
references: 20361007
references: Biochem Biophys Res Commun. 2009 Apr 10;381(3):350-4
references: 19233122
references: Biophys J. 2006 Aug 1;91(3):L23-5
references: 16751239
references: J Am Chem Soc. 2010 Nov 3;132(43):15112-5
references: 20932011
references: J Cell Biochem. 2012 Mar;113(3):956-66
references: 22034063
references: Biochemistry. 2010 Dec 21;49(50):10595-605
references: 21062093
references: J Am Chem Soc. 2006 Jun 7;128(22):7168-9
references: 16734463
references: Langmuir. 2005 Sep 27;21(20):9091-7
references: 16171337
references: J Am Chem Soc. 2007 Oct 24;129(42):12658-9
references: 17902674
references: PLoS One. 2011 Apr 27;6(4):e19414
references: 21556374
references: Phys Chem Chem Phys. 2010 Oct 7;12(37):11498-506
references: 20676431
references: Angew Chem Int Ed Engl. 2010 Mar 22;49(13):2319-23
references: 20209538
references: Langmuir. 2006 Jun 6;22(12):5341-9
references: 16732662
references: Chemphyschem. 2004 Mar 19;5(3):327-35
references: 15067869
references: Langmuir. 2009 Sep 1;25(17):10051-61
references: 19705898
references: J Pharm Sci. 2003 Sep;92(9):1754-72
references: 12949995
references: Chemphyschem. 2007 Feb 19;8(3):433-43
references: 17269116
references: Biochimie. 2000 May;82(5):409-20
references: 10865128
references: Plant J. 2007 Apr;50(2):207-18
references: 17355438
references: J Am Chem Soc. 2004 Jul 14;126(27):8376-7
references: 15237984
references: Free Radic Biol Med. 2006 Mar 15;40(6):940-51
references: 16540389
references: Eur Phys J E Soft Matter. 2009 Feb;28(2):211-20
references: 19101741
references: Biophys J. 1999 Sep;77(3):1445-57
references: 10465755
references: Circulation. 2007 Oct 23;116(17):1915-24
references: 17909102
references: Dev Dyn. 2008 Jan;237(1):18-27
references: 18058912
references: Bioelectrochemistry. 2002 May 15;56(1-2):171-3
references: 12009468
references: Science. 1996 Jan 5;271(5245):43-8
references: 8539599
references: J Biol Chem. 2001 Jun 22;276(25):22544-52
references: 11410600
references: Photochem Photobiol. 2006 Nov-Dec;82(6):1517-29
references: 16930094
references: J Pharm Sci. 2007 Jun;96(6):1490-503
references: 17094138
references: Pflugers Arch. 2008 Jan;455(4):575-82
references: 17638009
references: Biochemistry. 2002 Jan 22;41(3):697-705
references: 11790090
references: Langmuir. 2006 Dec 19;22(26):11267-74
references: 17154614
references: Chembiochem. 2009 Jul 20;10(11):1823-9
references: 19551796
references: Biophys J. 2005 Oct;89(4):2522-32
references: 16085770
references: Biochemistry. 1993 Aug 3;32(30):7703-11
references: 7688566
references: EMBO Rep. 2002 Oct;3(10):995-1001
references: 12231511
references: Biophys J. 2010 May 19;98(10):L50-2
references: 20483309
references: J Am Chem Soc. 2004 Jun 2;126(21):6512-3
references: 15161253
references: Bioessays. 2004 Sep;26(9):993-1004
references: 15351969
references: Environ Sci Technol. 2008 Oct 1;42(19):7496-501
references: 18939592
references: Biochemistry. 1978 Jul 25;17(15):3046-53
references: 698183
references: Annu Rev Cell Dev Biol. 2012;28:279-308
references: 23057743
references: J Am Chem Soc. 2004 Jul 28;126(29):8894-5
references: 15264810
references: Mol Biol Cell. 1999 May;10(5):1463-75
references: 10233156
references: J Biol Chem. 2010 May 14;285(20):15464-15475
references: 20220137
references: Biophys J. 1985 Jan;47(1):105-13
references: 3978184
references: J Phys Chem B. 2010 Jul 1;114(25):8291-300
references: 20504035
references: J Am Chem Soc. 2006 Mar 1;128(8):2711-4
references: 16492058
references: Anal Biochem. 2002 Aug 1;307(1):117-30
references: 12137788
references: Curr Cancer Drug Targets. 2009 Aug;9(5):639-51
references: 19508171
references: Br J Pharmacol. 1990 Jul;100(3):542-6
references: 2390678
references: J Phys Chem B. 2010 Mar 11;114(9):3334-40
references: 20163089
references: J Am Chem Soc. 2007 Jul 11;129(27):8420-1
references: 17579416
references: J Biol Chem. 2005 Dec 30;280(52):43030-8
references: 16243846
references: Mol Membr Biol. 2006 Jan-Feb;23(1):29-39
references: 16611578
references: J Biol Chem. 1994 Aug 12;269(32):20360-8
references: 8051131
references: Nature. 2012 Oct 11;490(7419):201-7
references: 23060190
references: J Biol Chem. 2002 Feb 22;277(8):6667-75
references: 11741921
references: Appl Spectrosc. 2010 Mar;64(3):275-81
references: 20223061
references: Biochim Biophys Acta. 1999 Aug 18;1439(3):317-30
references: 10446420
references: J Chem Phys. 2009 Oct 28;131(16):161107
references: 19894919
references: Science. 1997 Oct 31;278(5339):853-6
references: 9346482
references: Biochem Biophys Res Commun. 2006 Nov 24;350(3):604-9
references: 17027650
references: Anal Bioanal Chem. 2007 May;388(1):73-9
references: 17226005
references: J Exp Med. 2005 Jan 3;201(1):49-54
references: 15623571
references: Arterioscler Thromb Vasc Biol. 1997 Mar;17(3):445-53
references: 9102162
references: J Immunol. 2006 Dec 1;177(11):7849-57
references: 17114456
references: J Biol Chem. 2003 Jul 25;278(30):28109-15
references: 12736276
references: Microsc Res Tech. 2003 Apr 15;60(6):540-51
references: 12645002
references: Nature. 2005 Sep 29;437(7059):656-63
references: 16193040
references: Biochem Biophys Res Commun. 2005 Oct 7;335(4):1140-8
references: 16122705
references: J Biol Chem. 2001 Aug 17;276(33):30819-26
references: 11402046
references: Exp Cell Res. 2007 Sep 10;313(15):3308-18
references: 17643421
references: Traffic. 2010 Jun;11(6):813-26
references: 20230531
references: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9118-21
references: 15967988
references: Endocrinology. 2003 Mar;144(3):1062-73
references: 12586783
references: Thromb Haemost. 1999 Aug;82(2):748-54
references: 10605778
references: J Phys Chem C Nanomater Interfaces. 2011 Apr 21;115(15):7613-7620
references: 21712964
references: Thromb Haemost. 2001 Jul;86(1):266-75
references: 11487015
references: J Biol Chem. 2012 Feb 24;287(9):6941-8
references: 22215666
references: J Am Chem Soc. 2010 Apr 21;132(15):5405-12
references: 20337445
references: Biochem J. 1994 Mar 15;298 Pt 3:553-9
references: 7908188
references: J Phys Chem B. 2009 Nov 5;113(44):14816-23
references: 19824633
references: Semin Thromb Hemost. 2006 Apr;32 Suppl 1:61-8
references: 16673267
references: J Biol Chem. 2012 Aug 10;287(33):27659-69
references: 22730382
references: J Cell Biochem. 2008 Apr 1;103(5):1327-43
references: 17786931
references: Langmuir. 2010 May 4;26(9):6471-7
references: 19961170
references: Plant Physiol. 2012 Jul;159(3):1099-110
references: 22555879
references: Biochim Biophys Acta. 2007 Dec;1768(12):3080-9
references: 17991455
references: J Biomol NMR. 2005 Jul;32(3):257
references: 16132827
references: J Formos Med Assoc. 2010 Sep;109(9):632-40
references: 20863990
references: J Phys Chem A. 2009 Nov 12;113(45):12655-62
references: 19751059
references: J Mol Evol. 1997 Jan;44(1):43-56
references: 9010135
references: J Phys Chem B. 2006 Aug 10;110(31):15506-13
references: 16884274
references: Biochem Biophys Res Commun. 2006 Oct 13;349(1):192-9
references: 16930531
references: BMC Cancer. 2006 Dec 08;6:283
references: 17156439
references: J Biol Inorg Chem. 2003 Nov;8(8):803-9
references: 14517615
references: J Phys Chem B. 2011 May 26;115(20):6465-73
references: 21542565
references: Biophys J. 2008 Jul;95(1):186-93
references: 18339755
references: Microbes Infect. 2002 Apr;4(4):449-60
references: 11932196
references: Biochim Biophys Acta. 2009 Jan;1788(1):225-33
references: 18801332
references: J Am Chem Soc. 2010 Aug 18;132(32):11336-42
references: 20698700
references: Appl Spectrosc. 2009 May;63(5):528-37
references: 19470209
references: J Phys Chem B. 2009 Sep 10;113(36):12358-63
references: 19728722
references: Biomacromolecules. 2002 Jan-Feb;3(1):27-35
references: 11866552
references: J Chem Phys. 2005 Dec 1;123(21):211104
references: 16356031
references: Langmuir. 2007 Jul 3;23(14):7666-71
references: 17539668
references: Bioelectrochemistry. 2002 May 15;56(1-2):175-8
references: 12009469
references: Phys Rev Lett. 2009 Mar 6;102(9):095502
references: 19392531
references: Growth Factors. 2001;18(4):277-85
references: 11519826
references: EMBO J. 2003 Oct 15;22(20):5551-60
references: 14532127
references: Biomacromolecules. 2001 Spring;2(1):70-9
references: 11749157