title: "Omics" of human sperm: profiling protein phosphatases.
abstract: Phosphorylation is a major regulatory mechanism in eukaryotic cells performed by the concerted actions of kinases and phosphatases (PPs). Protein phosphorylation has long been relevant to sperm physiology, from acquisition of motility in the epididymis to capacitation in the female reproductive tract. While the precise kinases involved in the regulation of sperm phosphorylation have been studied for decades, the PPs have only recently received research interest. Tyrosine phosphorylation was first implicated in the regulation of several sperm-related functions, from capacitation to oocyte binding. Only afterwards, in 1996, the inhibition of the serine/threonine-PP phosphoprotein phosphatase 1 (PPP1) by okadaic acid and calyculin-A was shown to initiate motility in caput epididymal sperm. Today, the current mechanisms of sperm motility acquisition based on PPP1 and its regulators are still far from being fully understood. PPP1CC2, specifically expressed in mammalian sperm, has been considered to be the only sperm-specific serine/threonine-PP, while other PPP1 isoforms were thought to be absent from sperm. This article examines the "Omics" of human sperm, and reports, for the first time, the identification of three new serine/threonine-protein PPs, PPP1CB, PPP4C, and PPP6C, in human sperm, together with two tyrosine-PPs, MKP1 and PTP1C. We specifically localized in sperm PPP1CB and PPP1CC2 from the PPP1 subfamily, and PPP2CA, PPP4C, and PPP6C from the PPP2 subfamily of the serine/threonine-PPs. A semi-quantitative analysis was performed to determine the various PPs' differential expression in sperm head and tail. These findings contribute to a comprehensive understanding of human sperm PPs, and warrant further research for their clinical and therapeutic significance.
authors.affiliation: Centro de Biologia Celular, Secção Autónoma de Ciências da Saúde, Departamento de Biologia, Universidade de Aveiro, Aveiro, Portugal. mfardilha@ua.pt
authors.forename: Margarida
authors.initials: M
authors.lastname: Fardilha
authors.forename: Mónica
authors.initials: M
authors.lastname: Ferreira
authors.forename: Steven
authors.initials: S
authors.lastname: Pelech
authors.forename: Sandra
authors.initials: S
authors.lastname: Vieira
authors.forename: Sandra
authors.initials: S
authors.lastname: Rebelo
authors.forename: Luís
authors.initials: L
authors.lastname: Korrodi-Gregorio
authors.forename: Mário
authors.initials: M
authors.lastname: Sousa
authors.forename: Alberto
authors.initials: A
authors.lastname: Barros
authors.forename: Vladimiro
authors.initials: V
authors.lastname: Silva
authors.forename: Odete A B
authors.initials: OA
authors.lastname: da Cruz e Silva
authors.forename: Edgar F
authors.initials: EF
authors.lastname: da Cruz e Silva
mesh_terms: D057166:High-Throughput Screening Assays; D006801:Humans; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism; D021381:Protein Transport; D020543:Proteome; D040901:Proteomics / Q000379:methods; D015203:Reproducibility of Results; D013076:Sperm Count; D013081:Sperm Motility; D013094:Spermatozoa / Q000378:metabolism* / Q000502:physiology
chemical_list: D020543:Proteome; D010749:Phosphoprotein Phosphatases
references.citation: Dev Biol. 1999 Jan 1;205(1):98-110
references.pmid: 9882500
references.citation: FEBS Lett. 1987 Nov 2;223(2):340-6
references.pmid: 2822491
references.citation: Curr Med Chem. 2010;17(33):3996-4017
references.pmid: 20939825
references.citation: Sci Signal. 2008 Oct 14;1(41):pe44
references.pmid: 18922786
references.citation: Biochem Biophys Res Commun. 1993 Jul 30;194(2):930-7
references.pmid: 8393674
references.citation: Arch Androl. 2003 Sep-Oct;49(5):343-9
references.pmid: 12893510
references.citation: Prog Clin Biol Res. 1988;267:335-55
references.pmid: 2853368
references.citation: FEBS Lett. 1988 Dec 19;242(1):106-10
references.pmid: 2849555
references.citation: Biol Reprod. 2002 Dec;67(6):1936-42
references.pmid: 12444072
references.citation: Biol Reprod. 2003 Nov;69(5):1572-9
references.pmid: 12826576
references.citation: Mol Hum Reprod. 2002 Feb;8(2):124-35
references.pmid: 11818515
references.citation: Mol Endocrinol. 2002 Mar;16(3):630-9
references.pmid: 11875122
references.citation: Mol Neurodegener. 2010 Oct 11;5:40
references.pmid: 20937087
references.citation: Dev Biol. 1996 Nov 25;180(1):284-96
references.pmid: 8948591
references.citation: Biochem Pharmacol. 2011 Nov 15;82(10):1403-15
references.pmid: 21382349
references.citation: Andrologia. 2001 Nov;33(6):337-42
references.pmid: 11736793
references.citation: Curr Opin Cell Biol. 2005 Apr;17(2):197-202
references.pmid: 15780597
references.citation: Biol Reprod. 1996 Mar;54(3):709-18
references.pmid: 8835395
references.citation: Development. 1995 Apr;121(4):1129-37
references.pmid: 7743926
references.citation: Biol Reprod. 1996 Mar;54(3):719-27
references.pmid: 8835396
references.citation: Clin Immunol Immunopathol. 1994 Nov;73(2):168-79
references.pmid: 7923924
references.citation: J Reprod Infertil. 2011 Jul;12(3):193-9
references.pmid: 23926502
references.citation: Reproduction. 2003 Jan;125(1):17-26
references.pmid: 12622692
references.citation: J Proteome Res. 2009 Nov;8(11):5382-6
references.pmid: 19678645
references.citation: Biol Reprod. 2009 Jun;80(6):1239-52
references.pmid: 19211810
references.citation: Fertil Steril. 2007 Feb;87(2):436-8
references.pmid: 17074334
references.citation: Cell Tissue Res. 2012 Sep;349(3):765-82
references.pmid: 22427115
references.citation: Science. 1995 Jul 7;269(5220):83-6
references.pmid: 7541556
references.citation: FEBS Lett. 1987 Dec 21;226(1):176-8
references.pmid: 2826253
references.citation: Biol Reprod. 2004 Jul;71(1):177-84
references.pmid: 15028637
references.citation: J Androl. 1999 Jan-Feb;20(1):47-53
references.pmid: 10100473
references.citation: Dev Biol. 1997 Dec 15;192(2):340-50
references.pmid: 9441672
references.citation: J Reprod Dev. 2008 Jun;54(3):171-6
references.pmid: 18305366
references.citation: FEBS Lett. 1987 Sep 14;221(2):415-22
references.pmid: 3040474
references.citation: Biol Reprod. 1998 Jun;58(6):1476-89
references.pmid: 9623609
references.citation: Trends Biochem Sci. 1997 Jul;22(7):245-51
references.pmid: 9255065
references.citation: Mol Cell Proteomics. 2013 Feb;12(2):330-42
references.pmid: 23161514
references.citation: Reproduction. 2001 Sep;122(3):469-80
references.pmid: 11597312
references.citation: Curr Med Chem. 2002 Nov;9(22):2055-75
references.pmid: 12369870
references.citation: Asian J Androl. 2007 Jul;9(4):445-52
references.pmid: 17589781
references.citation: Am J Physiol Cell Physiol. 2011 Apr;300(4):C723-42
references.pmid: 21209361
references.citation: Dev Biol. 2004 Jan 15;265(2):399-415
references.pmid: 14732401
references.citation: Annu Rev Biophys Biomol Struct. 1998;27:133-64
references.pmid: 9646865
references.citation: Fertil Steril. 1994 Mar;61(3):536-41
references.pmid: 8137980
references.citation: J Biol Chem. 2003 Jul 11;278(28):26078-85
references.pmid: 12721286
references.citation: Mol Hum Reprod. 2011 Aug;17(8):466-77
references.pmid: 21257602
references.citation: Biol Reprod. 2007 Jun;76(6):992-1001
references.pmid: 17301292
references.citation: J Neurosci. 1995 May;15(5 Pt 1):3375-89
references.pmid: 7751917
references.citation: Biol Reprod. 1999 Nov;61(5):1184-97
references.pmid: 10529264
references.citation: Nat Cell Biol. 2002 May;4(5):E127-30
references.pmid: 11988757
references.citation: Fertil Steril. 1999 May;71(5):919-23
references.pmid: 10231057
references.citation: Hum Reprod. 2008 Apr;23(4):783-91
references.pmid: 18281682