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PMID: 21701840 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Protein tyrosine phosphatase non-receptor type 14 is a novel sperm-motility biomarker.

Journal of assisted reproduction and genetics ·Vol. 28 ·No. 9 ·2011-09-00 ·Pages 851-61

Chao HC, Chung CL, Pan HA, Liao PC, Kuo PL, Hsu CC

Abstract

To understand the molecular basis of sperm-motility and to identify related novel motility biomarkers. Two-dimensional electrophoresis (2DE) followed by Reverse-phase-nano-high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (RP-nano-HPLC-ESI-MS/MS) were applied to establish the human sperm proteome. Then the sperm proteome of moderate-motile human sperm fraction and that of good-motile human sperm fraction from pooled spermatozoa of forty normozoospermic donors (Group 1 subjects) were compared to identify the dysregulated proteins. Among these down-regulated proteins, Protein tyrosine phosphatase non-receptor type 14 (PTPN14) was chosen to reconfirm by Western blotting and semi-quantitative reverse transcription polymerase chain reaction. For clinical application, Western blotting and real-time reverse transcription polymerase chain reaction was performed to compare the expression level of PTPN14 in (Group 2 subjects) nine normozoospermic controls and thirty-three asthenozoospermic patients (including 21 mild asthenozoospermic cases and 12 severe cases). Finally, bioinformatic tools prediction and immunofluorescence assay were performed to elucidate the potential localization of PTPN14. The expression levels of three proteins were observed to be lower in the moderate-motile sperm fraction than in good-motile sperm of group 1 subjects. Among three proteins with persistent down-regulation in the moderate-motile sperm, we reconfirmed that the expression level of PTPN14 was significantly lower in both mRNA and protein levels from the moderate-motile sperm fraction. Further, down-regulation of PTPN14 was found at the translational and transcriptional level in the asthenozoospermic men. Finally, Bioinformatic tools prediction and immunofluorescence assay showed that PTPN14 maybe predominantly localized at the mitochondria in the midpiece of human ejaculated sperm. Proteomics tools were applied to identify three possible sperm motility-related proteins. Among these proteins, PTPN14 was highly likely a novel sperm-motility biomarker and a potential mitochondrial protein.

MeSH Terms
Adult Biomarkers/analysis,metabolism Chromatography, Liquid Chromatography, Reverse-Phase Electrophoresis, Gel, Two-Dimensional Humans Male Mitochondria/metabolism Protein Tyrosine Phosphatases, Non-Receptor/analysis,genetics,metabolism RNA, Messenger/metabolism Sperm Midpiece/metabolism Sperm Motility Spermatozoa/metabolism,physiology Tandem Mass Spectrometry
Chemicals
Biomarkers RNA, Messenger PTPN14 protein, human Protein Tyrosine Phosphatases, Non-Receptor
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Chao Hsin-Chih Albert
Division of Obstetrics and Gynecology, National Cheng Kung University College of Medicine and Hospital, Dou-Liou Branch, Yunlin, Taiwan.
Chung Chia-Ling
Pan Hsien-An
Liao Pao-Chi
Kuo Pao-Lin
Hsu Chao-Chin
References (50)
50 references, click to expand
  1. Linking genome and proteome by mass spectrometry: large-scale identification of yeast proteins from two dimensional gels.
    Proc Natl Acad Sci U S A. 1996 Dec 10;93(25):14440-5 PMID: 8962070
  2. Increased activity of the human sperm tyrosine kinase SRC by the cAMP-dependent pathway in the presence of calcium.
    Biol Reprod. 2008 Oct;79(4):657-66 PMID: 18562702
  3. Identification of several proteins involved in regulation of sperm motility by proteomic analysis.
    Fertil Steril. 2007 Feb;87(2):436-8 PMID: 17074334
  4. Asthenozoospermia: analysis of a large population.
    Arch Androl. 2003 Sep-Oct;49(5):343-9 PMID: 12893510
  5. Protein translocation into mitochondria: the role of TIM complexes.
    Trends Cell Biol. 2000 Jan;10(1):25-31 PMID: 10603473
  6. Crystal structure of human protein tyrosine phosphatase 14 (PTPN14) at 1.65-A resolution.
    Proteins. 2006 Jun 1;63(4):1132-6 PMID: 16534812
  7. Comprehensive proteomic analysis of bovine spermatozoa of varying fertility rates and identification of biomarkers associated with fertility.
    BMC Syst Biol. 2008 Feb 22;2:19 PMID: 18294385
  8. Requirement of protein tyrosine kinase and phosphatase activities for human sperm exocytosis.
    Dev Biol. 2004 Jan 15;265(2):399-415 PMID: 14732401
  9. The relation of computer-based measures of sperm morphology and motility to male infertility.
    Epidemiology. 1992 May;3(3):239-46 PMID: 1591323
  10. Redox regulation of tyrosine phosphorylation in human spermatozoa and its role in the control of human sperm function.
    J Cell Sci. 1995 May;108 ( Pt 5):2017-25 PMID: 7544800
  11. Tyrosine phosphorylation, thiol status, and protein tyrosine phosphatase in rat epididymal spermatozoa.
    Biol Reprod. 2004 Sep;71(3):1009-15 PMID: 15151929
  12. Investigation of human testis protein heterogeneity using 2-dimensional electrophoresis.
    J Androl. 2010 Jul-Aug;31(4):419-29 PMID: 20133968
  13. Interaction between Ca2+, cyclic 3',5' adenosine monophosphate, the superoxide anion, and tyrosine phosphorylation pathways in the regulation of human sperm capacitation.
    J Androl. 1998 Jul-Aug;19(4):434-43 PMID: 9733146
  14. Proteomic identification of human sperm proteins.
    Proteomics. 2006 Aug;6(15):4356-69 PMID: 16819732
  15. A novel signal transduction cascade in capacitating human spermatozoa characterised by a redox-regulated, cAMP-mediated induction of tyrosine phosphorylation.
    J Cell Sci. 1998 Mar;111 ( Pt 5):645-56 PMID: 9454738
  16. 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
  17. Motility and protein phosphorylation in healthy and asthenozoospermic sperm.
    J Proteome Res. 2009 Nov;8(11):5382-6 PMID: 19678645
  18. Human sperm hyperactivation and capacitation as parts of an oxidative process.
    Free Radic Biol Med. 1993 Feb;14(2):157-66 PMID: 8381103
  19. Identification of protein tyrosine phosphatases and dual-specificity phosphatases in mammalian spermatozoa and their role in sperm motility and protein tyrosine phosphorylation.
    Biol Reprod. 2009 Jun;80(6):1239-52 PMID: 19211810
  20. The prevalence of subfertility: a review of the current confusion and a report of two new studies.
    Fertil Steril. 1990 Dec;54(6):978-83 PMID: 2245856
  21. 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
  22. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding.
    Anal Biochem. 1976 May 7;72:248-54 PMID: 942051
  23. A redox-regulated tyrosine phosphorylation cascade in rat spermatozoa.
    J Androl. 2001 Jul-Aug;22(4):611-22 PMID: 11451358
  24. Protein tyrosine phosphatases in the human genome.
    Cell. 2004 Jun 11;117(6):699-711 PMID: 15186772
  25. Male infertility and mitochondrial DNA.
    Biochem Biophys Res Commun. 2004 Sep 10;322(1):333-9 PMID: 15313211
  26. Selective inhibition of protein tyrosine phosphatase activities by H2O2 and vanadate in vitro.
    Biochem Biophys Res Commun. 1992 Oct 30;188(2):773-9 PMID: 1445322
  27. Proteomic analysis of human pleural effusion.
    Proteomics. 2005 Mar;5(4):1062-74 PMID: 15682465
  28. Translocation of protein tyrosine phosphatase Pez/PTPD2/PTP36 to the nucleus is associated with induction of cell proliferation.
    J Cell Sci. 2000 Sep;113 ( Pt 17):3117-23 PMID: 10934049
  29. The characterization of human spermatozoa membrane proteins--surface antigens and immunological infertility.
    Electrophoresis. 1999 Apr-May;20(4-5):971-6 PMID: 10344274
  30. 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
  31. Comparative analysis of the Band 4.1/ezrin-related protein tyrosine phosphatase Pez from two Drosophila species: implications for structure and function.
    Gene. 2001 Sep 19;275(2):195-205 PMID: 11587846
  32. Regulation of phosphorylation level and distribution of PTP36, a putative protein tyrosine phosphatase, by cell-substrate adhesion.
    J Biol Chem. 1999 Jul 16;274(29):20717-24 PMID: 10400706
  33. Inhibition of protein tyrosine phosphatase-1B with antisense oligonucleotides improves insulin sensitivity and increases adiponectin concentrations in monkeys.
    Endocrinology. 2009 Apr;150(4):1670-9 PMID: 19164474
  34. Effects of overexpression of PTP36, a putative protein tyrosine phosphatase, on cell adhesion, cell growth, and cytoskeletons in HeLa cells.
    J Biol Chem. 1999 Apr 30;274(18):12905-9 PMID: 10212280
  35. 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
  36. Ontogeny of tyrosine phosphorylation-signaling pathways during spermatogenesis and epididymal maturation in the mouse.
    Biol Reprod. 2006 Oct;75(4):588-97 PMID: 16790687
  37. Mitochondria: more than just a powerhouse.
    Curr Biol. 2006 Jul 25;16(14):R551-60 PMID: 16860735
  38. Factors affecting the acrosome reaction in human spermatozoa.
    J Reprod Fertil. 1990 Sep;90(1):71-80 PMID: 2231556
  39. Capacitation-associated production of superoxide anion by human spermatozoa.
    Free Radic Biol Med. 1995 Mar;18(3):487-95 PMID: 9101239
  40. Plasma membrane-associated protein tyrosine phosphatase activity in hamster spermatozoa.
    Mol Reprod Dev. 1999 May;53(1):42-50 PMID: 10230815
  41. Role(s) of the serine/threonine protein phosphatase 1 on mammalian sperm motility.
    Arch Androl. 2007 Jul-Aug;53(4):169-77 PMID: 17852041
  42. 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
  43. Regulation of protein-tyrosine phosphorylation and human sperm capacitation by reactive oxygen derivatives.
    Free Radic Biol Med. 1997;22(4):643-56 PMID: 9013127
  44. Marked correlations in protein expression identified by proteomic analysis of human spermatozoa.
    Proteomics. 2007 Dec;7(23):4264-77 PMID: 18040982
  45. Regulation of sperm motility: emerging evidence for a major role for protein phosphatases.
    J Androl. 1994 Nov-Dec;15(6):505-9 PMID: 7721653
  46. Proteomics-based study on asthenozoospermia: differential expression of proteasome alpha complex.
    Mol Hum Reprod. 2010 Jul;16(7):452-62 PMID: 20304782
  47. Sperm-specific protein kinase A catalytic subunit Calpha2 orchestrates cAMP signaling for male fertility.
    Proc Natl Acad Sci U S A. 2004 Sep 14;101(37):13483-8 PMID: 15340140
  48. Identification of proteomic differences in asthenozoospermic sperm samples.
    Hum Reprod. 2008 Apr;23(4):783-91 PMID: 18281682
  49. Bicarbonate stimulation of boar sperm motility via a protein kinase A-dependent pathway: between-cell and between-ejaculate differences are not due to deficiencies in protein kinase A activation.
    J Androl. 2002 Jul-Aug;23(4):557-65 PMID: 12065464
  50. ERM proteins: head-to-tail regulation of actin-plasma membrane interaction.
    Trends Biochem Sci. 1997 Feb;22(2):53-8 PMID: 9048483
Article Info
Journal
Journal of assisted reproduction and genetics
Abbr.
J Assist Reprod Genet
ISSN
1573-7330
DOI
10.1007/s10815-011-9602-0
Published
2011-09-00
Epub
2011-00-24
Pages
851-61
Language
English
Region
Netherlands
NLM ID
9206495
PMCID
PMC3169687
Subset
IM
External Links
PubMed source DOI: 10.1007/s10815-011-9602-0 PMC Full Text View journal details
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