Home LiteratureArticle Details
PMID: 23194270 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Review

Sperm phosphoproteomics: historical perspectives and current methodologies.

Expert review of proteomics ·Vol. 9 ·No. 5 ·2012-10-00 ·Pages 533-48

Porambo JR, Salicioni AM, Visconti PE, Platt MD

Abstract

Mammalian sperm are differentiated germ cells that transfer genetic material from the male to the female. Owing to this essential role in the reproductive process, an understanding of the complex mechanisms that underlie sperm function has implications ranging from the development of novel contraceptives to the treatment of male infertility. While the importance of phosphorylation in sperm differentiation, maturation and fertilization has been well established, the ability to directly determine the sites of phosphorylation within sperm proteins and to quantitate the extent of phosphorylation at these sites is a recent development that has relied almost exclusively on advances in the field of proteomics. This review will summarize the work that has been carried out to date on sperm phosphoproteomics and discuss how the resulting qualitative and quantitative information has been used to provide insight into the manner in which protein phosphorylation events modulate sperm function. The authors also present the proteomics process as it is most often utilized for the elucidation of protein expression, with a particular emphasis on the way in which the process has been modified for the analysis of protein phosphorylation in sperm.

MeSH Terms
Fertilization Gene Expression Regulation Humans Infertility, Male/metabolism,pathology,therapy Male Mass Spectrometry Phosphoproteins/chemistry,metabolism Phosphorylation Proteomics/methods Spermatozoa/chemistry,metabolism
Chemicals
Phosphoproteins
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Porambo James R
Department of Chemistry and Chemical Biology, Troy, NY 12180-3590, USA.
Salicioni Ana M
Visconti Pablo E
Platt Mark D
References (111)
111 references, click to expand
  1. Mitochondria from ejaculated human spermatozoa do not synthesize proteins.
    FEBS Lett. 2003 Oct 9;553(1-2):205-8 PMID: 14550574
  2. Identification of 36 kDa phosphoprotein in fibrous sheath of hamster spermatozoa.
    Comp Biochem Physiol B Biochem Mol Biol. 2004 Apr;137(4):509-20 PMID: 15082001
  3. p95, the major phosphotyrosine-containing protein in mouse spermatozoa, is a hexokinase with unique properties.
    J Biol Chem. 1994 Feb 4;269(5):3810-7 PMID: 7508920
  4. Two-dimensional gel electrophoretic analysis of vectorially labeled surface proteins of human spermatozoa.
    Biol Reprod. 1997 Mar;56(3):771-87 PMID: 9047024
  5. Rapid identification of proteins by peptide-mass fingerprinting.
    Curr Biol. 1993 Jun 1;3(6):327-32 PMID: 15335725
  6. Collisions or electrons? Protein sequence analysis in the 21st century.
    Anal Chem. 2009 May 1;81(9):3208-15 PMID: 19364119
  7. Selective adsorption of phosphoproteins on gel-immobilized ferric chelate.
    Biochemistry. 1986 Nov 4;25(22):6850-3 PMID: 3801397
  8. Matrix-assisted laser desorption/ionization mass spectrometry of biopolymers.
    Anal Chem. 1991 Dec 15;63(24):1193A-1203A PMID: 1789447
  9. Sperm motility development in the epididymis is associated with decreased glycogen synthase kinase-3 and protein phosphatase 1 activity.
    Biol Reprod. 1996 Mar;54(3):709-18 PMID: 8835395
  10. Cyclic adenosine 3',5'monophosphate-dependent regulation of protein tyrosine phosphorylation in relation to human sperm capacitation and motility.
    Biol Reprod. 1996 Sep;55(3):684-92 PMID: 8862788
  11. Sample handling for proteome analysis.
    Electrophoresis. 1998 May;19(6):901-8 PMID: 9638936
  12. Capacitation of mouse spermatozoa. I. Correlation between the capacitation state and protein tyrosine phosphorylation.
    Development. 1995 Apr;121(4):1129-37 PMID: 7743926
  13. Response to: the problem with peptide presumption and low Mascot scoring.
    J Proteome Res. 2011 Nov 4;10(11):5272-3 PMID: 21942731
  14. A multidimensional electrospray MS-based approach to phosphopeptide mapping.
    Anal Chem. 2001 Feb 1;73(3):393-404 PMID: 11217738
  15. The mouse sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification.
    Proteomics. 2008 Apr;8(8):1720-30 PMID: 18340633
  16. Cyanate formation in solutions of urea. II. Effect of urea on the eye lens protein -crystallin.
    Biochim Biophys Acta. 1971 Sep 28;243(3):375-9 PMID: 5129585
  17. Identification of proteins undergoing tyrosine phosphorylation during mouse sperm capacitation.
    Int J Dev Biol. 2008;52(5-6):463-72 PMID: 18649259
  18. Novel fragmentation process of peptides by collision-induced decomposition in a tandem mass spectrometer: differentiation of leucine and isoleucine.
    Anal Chem. 1987 Nov 1;59(21):2621-5 PMID: 3688448
  19. Tyrosine phosphoproteome of hamster spermatozoa: role of glycerol-3-phosphate dehydrogenase 2 in sperm capacitation.
    Proteomics. 2009 Apr;9(7):1809-26 PMID: 19333995
  20. High resolution two-dimensional electrophoresis of proteins.
    J Biol Chem. 1975 May 25;250(10):4007-21 PMID: 236308
  21. Mapping the phosphorylation sites of proteins using on-line immobilized metal affinity chromatography/capillary electrophoresis/electrospray ionization multiple stage tandem mass spectrometry.
    Rapid Commun Mass Spectrom. 2000;14(17):1600-6 PMID: 10960913
  22. Probability-based protein identification by searching sequence databases using mass spectrometry data.
    Electrophoresis. 1999 Dec;20(18):3551-67 PMID: 10612281
  23. An approach to correlate tandem mass spectral data of peptides with amino acid sequences in a protein database.
    J Am Soc Mass Spectrom. 1994 Nov;5(11):976-89 PMID: 24226387
  24. Phosphopeptide analysis by on-line immobilized metal-ion affinity chromatography-capillary electrophoresis-electrospray ionization mass spectrometry.
    J Chromatogr A. 1999 Aug 20;853(1-2):225-35 PMID: 10486730
  25. Proteomic changes in mammalian spermatozoa during epididymal maturation.
    Asian J Androl. 2007 Jul;9(4):554-64 PMID: 17589795
  26. Identification of SRC as a key PKA-stimulated tyrosine kinase involved in the capacitation-associated hyperactivation of murine spermatozoa.
    J Cell Sci. 2006 Aug 1;119(Pt 15):3182-92 PMID: 16835269
  27. Identification of the proteins present in the bull sperm cytosolic fraction enriched in tyrosine kinase activity: a proteomic approach.
    Proteomics. 2006 Aug;6(16):4523-40 PMID: 16847872
  28. Phosphoprotein analysis using antibodies broadly reactive against phosphorylated motifs.
    J Biol Chem. 2002 Oct 18;277(42):39379-87 PMID: 12151408
  29. Cyclic AMP-dependent protein kinases of bovine epididymal spermatozoa.
    Biochem Biophys Res Commun. 1972 Sep 26;48(6):1131-8 PMID: 4342707
  30. Rapid PKA-catalysed phosphorylation of boar sperm proteins induced by the capacitating agent bicarbonate.
    Mol Reprod Dev. 2004 Mar;67(3):337-52 PMID: 14735495
  31. Simple and robust two-layer matrix/sample preparation method for MALDI MS/MS analysis of peptides.
    J Proteome Res. 2005 Sep-Oct;4(5):1709-16 PMID: 16212424
  32. A catalog of sperm histones.
    Genetics. 1969;61(1):Suppl:93-111 PMID: 5345404
  33. A cAMP-dependent phosphorylated motility protein in bovine epididymal sperm.
    J Biol Chem. 1980 Feb 10;255(3):982-7 PMID: 6243303
  34. [End amino acids of some protamines].
    Hoppe Seylers Z Physiol Chem. 1953;295:107-9 PMID: 13128702
  35. Evidence for the involvement of proline-directed serine/threonine phosphorylation in sperm capacitation.
    Mol Hum Reprod. 2006 Dec;12(12):781-9 PMID: 17050774
  36. Isolation and proteomic analysis of mouse sperm detergent-resistant membrane fractions: evidence for dissociation of lipid rafts during capacitation.
    Biol Reprod. 2005 Oct;73(4):721-9 PMID: 15917346
  37. Statistics notes. The odds ratio.
    BMJ. 2000 May 27;320(7247):1468 PMID: 10827061
  38. Protein kinase A and protein kinase C(alpha)/PPP1CC2 play opposing roles in the regulation of phosphatidylinositol 3-kinase activation in bovine sperm.
    Reproduction. 2010 Jul;140(1):43-56 PMID: 20442273
  39. Identification of 36-kDa flagellar phosphoproteins associated with hamster sperm motility.
    J Biochem. 2003 Mar;133(3):361-9 PMID: 12761172
  40. Progress with proteome projects: why all proteins expressed by a genome should be identified and how to do it.
    Biotechnol Genet Eng Rev. 1996;13:19-50 PMID: 8948108
  41. Fragmentation of phosphopeptides in an ion trap mass spectrometer.
    J Am Soc Mass Spectrom. 1998 Nov;9(11):1175-88 PMID: 9794085
  42. Cyanate formation in solutions of urea. I. Calculation of cyanate concentrations at different temperature and pH.
    Biochim Biophys Acta. 1971 Sep 28;243(3):366-73 PMID: 5129584
  43. Isoelectric focusing in pH gradients--a technique for fractionation and characterization of ampholytes.
    Methods Biochem Anal. 1971;19:1-104 PMID: 4935451
  44. SIMAC (sequential elution from IMAC), a phosphoproteomics strategy for the rapid separation of monophosphorylated from multiply phosphorylated peptides.
    Mol Cell Proteomics. 2008 Apr;7(4):661-71 PMID: 18039691
  45. Multiple glycolytic enzymes are tightly bound to the fibrous sheath of mouse spermatozoa.
    Biol Reprod. 2006 Aug;75(2):270-8 PMID: 16687649
  46. Immobilized metal ion affinity chromatography.
    Protein Expr Purif. 1992 Aug;3(4):263-81 PMID: 1422221
  47. Evaluation of algorithms for protein identification from sequence databases using mass spectrometry data.
    Proteomics. 2004 Mar;4(3):619-28 PMID: 14997485
  48. 95 kd sperm proteins bind ZP3 and serve as tyrosine kinase substrates in response to zona binding.
    Cell. 1989 Jun 30;57(7):1123-30 PMID: 2472220
  49. Andromeda: a peptide search engine integrated into the MaxQuant environment.
    J Proteome Res. 2011 Apr 1;10(4):1794-805 PMID: 21254760
  50. Isolation and identification of sperm membrane antigens recognized by antisperm antibodies, and their possible role in immunological infertility disease.
    Mol Hum Reprod. 2001 Feb;7(2):113-8 PMID: 11160836
  51. Extracellular signal-regulated kinases modulate capacitation of human spermatozoa.
    Biol Reprod. 1998 Jun;58(6):1476-89 PMID: 9623609
  52. Electrospray ionization for mass spectrometry of large biomolecules.
    Science. 1989 Oct 6;246(4926):64-71 PMID: 2675315
  53. Characterization and use of monoclonal antibodies for isolation of phosphotyrosyl proteins from retrovirus-transformed cells and growth factor-stimulated cells.
    Mol Cell Biol. 1983 Aug;3(8):1343-52 PMID: 6194425
  54. Fragmentation of protonated peptides: surface-induced dissociation in conjunction with a quantum mechanical approach.
    Anal Chem. 1993 Oct 15;65(20):2859-72 PMID: 8250266
  55. Phosphoric acid enhances the performance of Fe(III) affinity chromatography and matrix-assisted laser desorption/ionization tandem mass spectrometry for recovery, detection and sequencing of phosphopeptides.
    Rapid Commun Mass Spectrom. 2004;18(15):1721-30 PMID: 15282771
  56. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae.
    Nat Biotechnol. 2002 Mar;20(3):301-5 PMID: 11875433
  57. Immobilized metal ion affinity adsorption and immobilized metal ion affinity chromatography of biomaterials. Serum protein affinities for gel-immobilized iron and nickel ions.
    Biochemistry. 1983 Mar 29;22(7):1621-30 PMID: 6849872
  58. The Orbitrap: a new mass spectrometer.
    J Mass Spectrom. 2005 Apr;40(4):430-43 PMID: 15838939
  59. Transmembrane adenylyl cyclase regulates amphibian sperm motility through protein kinase A activation.
    Dev Biol. 2011 Feb 1;350(1):80-8 PMID: 21126515
  60. Immobilized gallium(III) affinity chromatography of phosphopeptides.
    Anal Chem. 1999 Jul 15;71(14):2883-92 PMID: 10424175
  61. Silver staining of proteins in polyacrylamide gels.
    Anal Biochem. 1981 Nov 15;118(1):197-203 PMID: 6175245
  62. Analysis of proteomic changes associated with sperm capacitation through the combined use of IPG-strip pre-fractionation followed by RP chromatography LC-MS/MS analysis.
    Proteomics. 2010 Feb;10(3):482-95 PMID: 19943266
  63. Recent developments in ion-trap mass spectrometry and related technologies.
    Expert Rev Proteomics. 2006 Feb;3(1):143-51 PMID: 16445358
  64. Kinomics: methods for deciphering the kinome.
    Nat Methods. 2005 Jan;2(1):17-25 PMID: 15789031
  65. Phosphoproteome analysis of capacitated human sperm. Evidence of tyrosine phosphorylation of a kinase-anchoring protein 3 and valosin-containing protein/p97 during capacitation.
    J Biol Chem. 2003 Mar 28;278(13):11579-89 PMID: 12509440
  66. Epididymal secreted protein Crisp-1 and sperm function.
    Mol Cell Endocrinol. 2006 May 16;250(1-2):122-7 PMID: 16414181
  67. Multiplexed protein quantitation in Saccharomyces cerevisiae using amine-reactive isobaric tagging reagents.
    Mol Cell Proteomics. 2004 Dec;3(12):1154-69 PMID: 15385600
  68. Label-free quantitation of phosphopeptide changes during rat sperm capacitation.
    J Proteome Res. 2010 Feb 5;9(2):718-29 PMID: 19947656
  69. The rat sperm proteome characterized via IPG strip prefractionation and LC-MS/MS identification.
    Proteomics. 2008 Jun;8(11):2312-21 PMID: 18528845
  70. Metal chelate affinity chromatography, a new approach to protein fractionation.
    Nature. 1975 Dec 18;258(5536):598-9 PMID: 1678
  71. Is proteomics the new genomics?
    Cell. 2007 Aug 10;130(3):395-8 PMID: 17693247
  72. High-resolution mass spectrometers.
    Annu Rev Anal Chem (Palo Alto Calif). 2008;1:579-99 PMID: 20636090
  73. A two-dimensional quadrupole ion trap mass spectrometer.
    J Am Soc Mass Spectrom. 2002 Jun;13(6):659-69 PMID: 12056566
  74. Quantitative analysis of complex protein mixtures using isotope-coded affinity tags.
    Nat Biotechnol. 1999 Oct;17(10):994-9 PMID: 10504701
  75. Enhanced detection of phosphopeptides in matrix-assisted laser desorption/ionization mass spectrometry using ammonium salts.
    J Am Soc Mass Spectrom. 1999 Jan;10(1):35-44 PMID: 9888183
  76. Identification of the 58-kDa phosphoprotein associated with motility initiation of hamster spermatozoa.
    J Biochem. 2003 Oct;134(4):559-65 PMID: 14607983
  77. The extracellular signal-regulated kinase (ERK) pathway is involved in human sperm function and modulated by the superoxide anion.
    Mol Hum Reprod. 2002 Feb;8(2):124-35 PMID: 11818515
  78. Use of titanium dioxide to find phosphopeptide and total protein changes during epididymal sperm maturation.
    J Proteome Res. 2011 Mar 4;10(3):1004-17 PMID: 21155529
  79. Ion channels, phosphorylation and mammalian sperm capacitation.
    Asian J Androl. 2011 May;13(3):395-405 PMID: 21540868
  80. Regulation of protein tyrosine phosphorylation during bovine sperm capacitation by a cyclic adenosine 3'5'-monophosphate-dependent pathway.
    Biol Reprod. 1997 Mar;56(3):707-19 PMID: 9047017
  81. Capacitation of mouse spermatozoa. II. Protein tyrosine phosphorylation and capacitation are regulated by a cAMP-dependent pathway.
    Development. 1995 Apr;121(4):1139-50 PMID: 7538069
  82. Peptide and protein sequence analysis by electron transfer dissociation mass spectrometry.
    Proc Natl Acad Sci U S A. 2004 Jun 29;101(26):9528-33 PMID: 15210983
  83. Contributions of mass spectrometry to peptide and protein structure.
    Biomed Environ Mass Spectrom. 1988 Oct;16(1-12):99-111 PMID: 3072035
  84. CABYR isoforms expressed in late steps of spermiogenesis bind with AKAPs and ropporin in mouse sperm fibrous sheath.
    Reprod Biol Endocrinol. 2010 Aug 23;8:101 PMID: 20731842
  85. Tandem mass spectrometry identifies proteins phosphorylated by cyclic AMP-dependent protein kinase when sea urchin sperm undergo the acrosome reaction.
    Dev Biol. 2005 Sep 1;285(1):116-25 PMID: 16038896
  86. Statistical characterization of ion trap tandem mass spectra from doubly charged tryptic peptides.
    Anal Chem. 2003 Mar 1;75(5):1155-63 PMID: 12641236
  87. Establishment of a high-resolution 2-D reference map of human spermatozoal proteins from 12 fertile sperm-bank donors.
    Asian J Androl. 2007 May;9(3):321-9 PMID: 17486272
  88. Tissue-specific PKA inhibition using a chemical genetic approach and its application to studies on sperm capacitation.
    Proc Natl Acad Sci U S A. 2008 Dec 30;105(52):20740-5 PMID: 19074277
  89. The development of the DIGE system: 2D fluorescence difference gel analysis technology.
    Anal Bioanal Chem. 2005 Jun;382(3):669-78 PMID: 15900442
  90. Optimization of electron transfer dissociation via informed selection of reagents and operating parameters.
    Anal Chem. 2012 Feb 7;84(3):1781-5 PMID: 22182179
  91. Regulation of protein tyrosine phosphorylation in boar sperm through a cAMP-dependent pathway.
    Mol Reprod Dev. 1998 Nov;51(3):304-14 PMID: 9771651
  92. Development and applications of in-gel CNBr/tryptic digestion combined with mass spectrometry for the analysis of membrane proteins.
    J Proteome Res. 2003 Sep-Oct;2(5):543-52 PMID: 14582651
  93. Micro-electrospray mass spectrometry: Ultra-high-sensitivity analysis of peptides and proteins.
    J Am Soc Mass Spectrom. 1994 Jul;5(7):605-13 PMID: 24221962
  94. Inhibition of Ser/Thr phosphatases induces capacitation-associated signaling in the presence of Src kinase inhibitors.
    J Biol Chem. 2010 Mar 12;285(11):7977-85 PMID: 20068039
  95. Analysis of the human sperm proteome.
    Ann N Y Acad Sci. 2005 Dec;1061:190-202 PMID: 16467268
  96. A protein sequenator.
    Eur J Biochem. 1967 Mar;1(1):80-91 PMID: 6059350
  97. Identification of post-translational modifications that occur during sperm maturation using difference in two-dimensional gel electrophoresis.
    Proteomics. 2005 Mar;5(4):1003-12 PMID: 15712234
  98. FSP95, a testis-specific 95-kilodalton fibrous sheath antigen that undergoes tyrosine phosphorylation in capacitated human spermatozoa.
    Biol Reprod. 1999 Nov;61(5):1184-97 PMID: 10529264
  99. Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS.
    Anal Chem. 2003 Apr 15;75(8):1895-904 PMID: 12713048
  100. Use of differential isotopic labeling and mass spectrometry to analyze capacitation-associated changes in the phosphorylation status of mouse sperm proteins.
    J Proteome Res. 2009 Mar;8(3):1431-40 PMID: 19186949
  101. Less label, more free: approaches in label-free quantitative mass spectrometry.
    Proteomics. 2011 Feb;11(4):535-53 PMID: 21243637
  102. Highly selective enrichment of phosphorylated peptides from peptide mixtures using titanium dioxide microcolumns.
    Mol Cell Proteomics. 2005 Jul;4(7):873-86 PMID: 15858219
  103. Model studies on iron(III) ion affinity chromatography. II. Interaction of immobilized iron(III) ions with phosphorylated amino acids, peptides and proteins.
    J Chromatogr. 1992 Jun 26;604(1):19-28 PMID: 1639926
  104. Differential extraction and enrichment of human sperm surface proteins in a proteome: identification of immunocontraceptive candidates.
    Electrophoresis. 2001 Aug;22(14):3053-66 PMID: 11565800
  105. Monitoring protein kinase and phosphatase reactions with matrix-assisted laser desorption/ionization mass spectrometry and capillary zone electrophoresis: comparison of the detection efficiency of peptide-phosphopeptide mixtures.
    Biol Mass Spectrom. 1994 Aug;23(8):519-28 PMID: 7918694
  106. Decision tree-driven tandem mass spectrometry for shotgun proteomics.
    Nat Methods. 2008 Nov;5(11):959-64 PMID: 18931669
  107. Basic local alignment search tool.
    J Mol Biol. 1990 Oct 5;215(3):403-10 PMID: 2231712
  108. Enhanced ionization of phosphorylated peptides during MALDI TOF mass spectrometry.
    Anal Chem. 2004 Mar 1;76(5):1532-6 PMID: 14987115
  109. Identification of the human testis protein phosphatase 1 interactome.
    Biochem Pharmacol. 2011 Nov 15;82(10):1403-15 PMID: 21382349
  110. Epididymal protein targets: a brief history of the development of epididymal protease inhibitor as a contraceptive.
    J Androl. 2011 Nov-Dec;32(6):698-704 PMID: 21441428
  111. Phosphorylation of protamine during spermatogenesis in trout testis.
    Proc Natl Acad Sci U S A. 1967 Sep;58(3):1011-8 PMID: 5233832
Article Info
Journal
Expert review of proteomics
Abbr.
Expert Rev Proteomics
ISSN
1744-8387
Published
2012-10-00
Pages
533-48
Language
English
Region
England
NLM ID
101223548
PMCID
PMC3561639
Subset
IM
Grants
NICHD NIH HHS · R01 HD038082 · United States
NICHD NIH HHS · R01 HD044044 · United States
NICHD NIH HHS · HD38082 · United States
NICHD NIH HHS · HD44044 · United States
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]