title: Mass spectrometry of membrane proteins: a focus on aquaporins.
abstract: Membrane proteins are abundant, critically important biomolecules that conduct essential functions in all cells and are the targets of a significant number of therapeutic drugs. However, the analysis of their expression, modification, protein-protein interactions, and structure by mass spectrometry has lagged behind similar studies of soluble proteins. Here we review the limitations to analysis of integral membrane and membrane-associated proteins and highlight advances in sample preparation and mass spectrometry methods that have led to the successful analysis of this protein class. Advances in the analysis of membrane protein posttranslational modification, protein-protein interaction, protein structure, and tissue distributions by imaging mass spectrometry are discussed. Furthermore, we focus our discussion on the application of mass spectrometry for the analysis of aquaporins as a prototypical integral membrane protein and how advances in analytical methods have revealed new biological insights into the structure and function of this family of proteins.
authors: Department of Biochemistry, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, United States. kevin.schey@vanderbilt.edu
authors: Kevin L
authors: KL
authors: Schey
authors: Angus C
authors: AC
authors: Grey
authors: Joshua J
authors: JJ
authors: Nicklay
mesh_terms: D000215:Acylation; D000818:Animals; D020346:Aquaporins / Q000032:analysis*; D005227:Fatty Acids / Q000378:metabolism; D006801:Humans; D007553:Isotope Labeling / Q000379:methods; D013058:Mass Spectrometry / Q000379:methods*; D008565:Membrane Proteins / Q000032:analysis / Q000302:isolation & purification; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D020346:Aquaporins; D005227:Fatty Acids; D008565:Membrane Proteins
references: Anal Chem. 2010 Jul 1;82(13):5415-9
references: 20518534
references: J Mol Biol. 2012 Feb 24;416(3):400-13
references: 22227391
references: Anal Biochem. 1993 Sep;213(2):256-63
references: 8238899
references: EMBO Mol Med. 2012 Jan;4(1):15-26
references: 22095752
references: Proc Natl Acad Sci U S A. 2006 May 2;103(18):7159-64
references: 16641100
references: Anal Chem. 2003 Apr 15;75(8):1895-904
references: 12713048
references: Anal Chem. 2000 Nov 15;72(22):5655-8
references: 11101244
references: Mol Cell Proteomics. 2011 Feb;10(2):M000031-MCP201
references: 20360033
references: Exp Eye Res. 2011 Dec;93(6):912-20
references: 22036630
references: J Cell Biol. 2008 Aug 11;182(3):587-601
references: 18678705
references: J Proteome Res. 2006 Sep;5(9):2339-47
references: 16944946
references: J Biol Chem. 2009 Apr 10;284(15):10110-9
references: 19203996
references: J Mol Biol. 2004 Sep 24;342(4):1337-45
references: 15351655
references: J Biol Chem. 2004 Jan 23;279(4):2975-83
references: 14593099
references: Expert Rev Proteomics. 2011 Aug;8(4):483-94
references: 21819303
references: Methods. 2011 Dec;55(4):330-6
references: 21982782
references: Biochem Biophys Res Commun. 2005 May 20;330(4):1041-7
references: 15823548
references: Anal Chem. 2009 Aug 15;81(16):6563-71
references: 20337372
references: J Proteome Res. 2009 Jul;8(7):3278-83
references: 19326924
references: Biochem Biophys Res Commun. 2009 Dec 18;390(3):1034-9
references: 19857466
references: Annu Rev Biochem. 2007;76:167-93
references: 17328674
references: J Biol Chem. 2009 May 29;284(22):14683-7
references: 19193633
references: Mol Cell Proteomics. 2002 Jan;1(1):46-59
references: 12096140
references: Mol Cell Proteomics. 2004 Jul;3(7):729-35
references: 15102926
references: Proteomics. 2008 Nov;8(21):4466-83
references: 18972526
references: Proteins. 2000 Jun 1;39(4):417-20
references: 10813823
references: Methods Mol Biol. 2008;432:389-401
references: 18370032
references: Invest Ophthalmol Vis Sci. 2000 Jan;41(1):175-82
references: 10634618
references: Biochim Biophys Acta. 2008 Apr;1778(4):1181-9
references: 18179769
references: Proteomics. 2008 Oct;8(19):4066-82
references: 18763707
references: Biochemistry. 2010 Nov 16;49(45):9858-65
references: 20942504
references: Structure. 2012 May 9;20(5):826-40
references: 22579250
references: J Am Chem Soc. 2011 Dec 21;133(50):20237-44
references: 22043856
references: J Proteomics. 2010 Oct 10;73(11):2078-91
references: 20797458
references: Age (Dordr). 2011 Dec;33(4):543-54
references: 21181282
references: Protein Sci. 1998 Jun;7(6):1423-30
references: 9655347
references: Subcell Biochem. 2007;43:35-47
references: 17953390
references: Nat Biotechnol. 2001 Mar;19(3):242-7
references: 11231557
references: Anal Chem. 2012 Sep 4;84(17):7469-78
references: 22880955
references: Proc Natl Acad Sci U S A. 2003 Jun 10;100(12):6940-5
references: 12771378
references: Protein Sci. 1998 Mar;7(3):758-64
references: 9541408
references: J Biol Chem. 2008 Jul 25;283(30):21278-83
references: 18508773
references: Invest Ophthalmol Vis Sci. 2008 Mar;49(3):1030-6
references: 18326727
references: Trends Biochem Sci. 2011 Jul;36(7):388-96
references: 21616670
references: Invest Ophthalmol Vis Sci. 2005 Apr;46(4):1393-402
references: 15790907
references: Invest Ophthalmol Vis Sci. 2006 Apr;47(4):1562-70
references: 16565393
references: Nat Biotechnol. 2001 Oct;19(10):946-51
references: 11581660
references: Biochemistry. 2004 Sep 7;43(35):11145-52
references: 15366924
references: Curr Opin Chem Biol. 2004 Oct;8(5):519-26
references: 15450495
references: Mol Cell Proteomics. 2010 May;9(5):791-803
references: 20093275
references: Nature. 2008 Jun 26;453(7199):1266-70
references: 18500332
references: Anal Chem. 1997 Dec 1;69(23):4751-60
references: 9406525
references: Nature. 2011 Oct 30;480(7376):254-8
references: 22037311
references: Biochemistry. 2004 Aug 3;43(30):9856-65
references: 15274640
references: Anal Chem. 2011 Oct 1;83(19):7234-41
references: 21770468
references: J Proteome Res. 2009 Mar;8(3):1540-54
references: 19209902
references: J Proteome Res. 2009 Mar;8(3):1565-76
references: 19199705
references: Annu Rev Biochem. 2011;80:247-71
references: 21548785
references: J Proteomics. 2010 Mar 10;73(5):868-78
references: 20096812
references: Expert Rev Proteomics. 2004 Aug;1(2):153-63
references: 15966810
references: Annu Rev Med. 2012;63:303-16
references: 22248325
references: Mol Cell Proteomics. 2004 Dec;3(12):1154-69
references: 15385600
references: Science. 2008 Jul 11;321(5886):243-6
references: 18556516
references: Biochemistry. 2008 Jan 8;47(1):339-47
references: 18081321
references: Invest Ophthalmol Vis Sci. 1997 Nov;38(12):2508-15
references: 9375569
references: Biochemistry. 2008 Jan 8;47(1):73-83
references: 18052347
references: Proteomics. 2004 Jan;4(1):31-45
references: 14730670
references: Proteomics. 2008 Sep;8(18):3895-905
references: 18712767
references: Biochem J. 1997 Sep 15;326 ( Pt 3):799-806
references: 9307030
references: Nat Biotechnol. 2003 May;21(5):532-8
references: 12692561
references: Semin Immunopathol. 2011 Sep;33(5):441-54
references: 21688197
references: Anal Chem. 2012 Jun 19;84(12):5186-91
references: 22607469
references: J Am Chem Soc. 2012 Nov 14;134(45):18724-31
references: 23075429
references: Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9528-33
references: 15210983
references: Am J Physiol Cell Physiol. 2005 Nov;289(5):C1303-11
references: 16107506
references: J Proteome Res. 2008 Jul;7(7):2696-702
references: 18489132
references: Clin Dev Immunol. 2011;2011:842849
references: 22190973
references: Trends Biochem Sci. 2005 Oct;30(10):551-8
references: 16125387
references: J Am Soc Mass Spectrom. 2008 Jun;19(6):814-22
references: 18396059
references: Angew Chem Int Ed Engl. 2004 Aug 20;43(33):4278-90
references: 15368374
references: J Am Soc Mass Spectrom. 2007 Aug;18(8):1429-38
references: 17544294
references: Invest Ophthalmol Vis Sci. 2013 Feb 07;54(2):1135-43
references: 23349431
references: Structure. 2008 Sep 10;16(9):1389-98
references: 18786401
references: Analyst. 2010 Jun;135(6):1191-200
references: 20498872
references: Anal Chem. 2013 Feb 5;85(3):1880-8
references: 23305238
references: Exp Eye Res. 2009 May;88(5):966-73
references: 19135052
references: Anal Chem. 2010 Jul 1;82(13):5760-7
references: 20521825
references: Methods Mol Biol. 2009;528:327-38
references: 19153703
references: Nature. 2004 May 13;429(6988):193-7
references: 15141214
references: Proteomics. 2008 Oct;8(19):3991-4011
references: 18780351
references: J Proteome Res. 2008 Dec;7(12):5286-94
references: 18939861
references: Nat Biotechnol. 2003 Mar;21(3):262-7
references: 12610573
references: Invest Ophthalmol Vis Sci. 2011 Jul 07;52(8):5079-87
references: 21642618
references: J Biol Chem. 2011 Sep 9;286(36):31915-23
references: 21733844
references: J Proteome Res. 2004 Jul-Aug;3(4):807-12
references: 15359735
references: J Cell Mol Med. 2006 Apr-Jun;10(2):364-75
references: 16796805
references: Curr Opin Struct Biol. 2008 Apr;18(2):229-35
references: 18194855
references: Hepatology. 2006 Feb;43(2):287-96
references: 16440338
references: Adv Exp Med Biol. 2010;679:1-17
references: 20666220
references: Curr Eye Res. 2008 Aug;33(8):621-9
references: 18696337
references: Biophys J. 1992 Nov;63(5):1240-3
references: 1477275
references: Traffic. 2011 Dec;12(12):1659-68
references: 21645191
references: J Mol Biol. 2009 Dec 18;394(5):968-81
references: 19804782
references: Mol Cell Proteomics. 2012 Mar;11(3):M111.013722
references: 22021278