PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis

MacLeod, Graham; Shang, Peng; Booth, Gregory T.; Mastropaolo, Lucas A.; Manafpoursakha, Niloufar; Vogl, A. Wayne; Varmuza, Susannah

doi:10.1530/rep-13-0224

Cited by 15 publications

(10 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Mammalian seminal plasma originates from multiple cellular sources in the male genital tract including testis, epididymis, vas deferens, vesicular glands, prostate gland and other accessory sexual glands. Seminal plasma contains a high concentration of subcellular lipid-bound microparticles (extracellular vesicles) which have been identified to encompass a complex composition of lipids, mRNAs, microRNAs and proteins [ 12 , 19 ]. Exosome-like vesicles have also been isolated from the seminal plasma of rat [ 20 ], rabbit [ 21 ], ram [ 22 ], bull [ 23 ], stallion [ 24 ], and boar [ 10 ].…”

Section: Discussionmentioning

confidence: 99%

“…Seminal plasma exosomes are membrane vesicles ranging from 30 to 120-nm diameter in size that are produced by organs in the male genital tracts including epididymis and prostate [ 10 , 14 , 15 ]. In boar, seminal plasma exosomes could inhibit the capacitation-dependent cholesterol efflux and mediate degradation of the 14-kD phosphorylated polypeptide of capacitated sperm [ 10 , 12 ]. Several previous studies have demonstrated that seminal plasma exosomes may play an important role in maintaining the sperm function during in vitro preservation.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Boar seminal plasma exosomes maintain sperm function by infiltrating into the sperm membrane

et al. 2016

View full text Add to dashboard Cite

Seminal plasma ingredients are important for maintenance of sperm viability. This study focuses on the effect of boar seminal plasma exosomes on sperm function during long-term liquid storage. Boar seminal plasma exosomes had typical nano-structure morphology as measured by scanning electron microscopy (SEM) and molecular markers such as AWN, CD9 and CD63 by western blot analysis. The effect on sperm parameters of adding different ratio of boar seminal plasma exosomes to boar sperm preparations was analyzed. Compared to the diluent without exosomes, the diluent with four times or sixteen times exosomes compared to original semen had higher sperm motility, prolonged effective survival time, improved sperm plasma membrane integrity (p < 0.05), increased total antioxidant capacity (T-AOC) activity and decreased malondialdehyde (MDA) content. The diluent containing four times concentration of exosomes compared to original semen was determined to inhibit premature capacitation, but not to influence capacitation induced in vitro. Inhibition of premature capacitation is likely related to the concentration of exosomes which had been demonstrated to transfer proteins including AWN and PSP-1 into sperm. In addition, using fluorescence microscopy and scanning electron microscopy analysis, it was demonstrated that exosomes in diluent were directly binding to the membrane of sperm head which could improve sperm plasma membrane integrity.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Boar seminal plasma exosomes maintain sperm function by infiltrating into the sperm membrane

et al. 2016

View full text Add to dashboard Cite

show abstract

“…Considering the respective localization of TSSK1 and TSSK2 ([ 23 ] and Figure 2 ) as well as the high homology between TSSK1 and TSSK2, it is not possible to rule out that SPAGL interacts with TSSK1. In addition to its putative interaction with SPAGL, TSSK1 was found to interact with the testis-specific phosphatase isoform PPP1CC2 [ 58 ]. These authors provided evidence indicating that PPP1CC2 interaction with TSSK1 is indirect, by forming a triad with TSKS, and proposed that this testicular kinase/phosphatase complex plays a critical role in normal development of sperm mitochondrial sheath during spermatogenesis.…”

Section: In Vitro Biochemical Characterization Of Tssk Kinasesmentioning

confidence: 99%

Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception†

Salicioni

Gervasi

Sosnik

et al. 2020

Biology of Reproduction

View full text Add to dashboard Cite

Male contraception is a very active area of research. Several hormonal agents have entered clinical trials, while potential non-hormonal targets have been brought to light more recently and are at earlier stages of development. The general strategy is to target genes along the molecular pathways of sperm production, maturation, or function, and it is predicted that these novel approaches will hopefully lead to more selective male contraceptive compounds with a decreased side effect burden. Protein kinases are known to play a major role in signaling events associated with sperm differentiation and function. In this review, we focus our analysis on the testis-specific serine kinase (TSSK) protein family. We have previously shown that members of the family of TSSKs are postmeiotically expressed in male germ cells and in mature mammalian sperm. The restricted postmeiotic expression of TSSKs as well as the importance of phosphorylation in signaling processes strongly suggests that TSSKs have an important role in germ cell differentiation and/or sperm function. This prediction has been supported by the reported sterile phenotype of the Tssk6 knockout (KO) mice and of the double Tssk1 and Tssk2 KO mice and by the male subfertile phenotype observed in a Tssk4 KO mouse model. Summary Sentence The established role of TSSKs in spermiogenesis and in male fertility, together with their unique kinase features, strongly supports this family of protein kinases as a very promising drug discovery target for development of a non-hormonal male contraceptive.

show abstract

“…This dual role of PP1γ2 is intriguing because loss of the enzymes of cAMP metabolism and action, sAC or PKA in testis, does not impair sperm morphogenesis or sperm formation. It is likely that other serine/threonine protein kinases along with PP1γ2 are responsible for regulation of protein phosphorylation during spermatogenesis (Kawa et al, 2006;Xu et al, 2007;MacLeod et al, 2014;Cruz et al, 2019). Due to its requirement in spermatogenesis, it is not possible to obtain sperm lacking PP1γ2, which is a limitation for the study of the enzyme in mature sperm.…”

Section: Protein Phosphatase Isoform Pp1γ2 In Sperm Functionmentioning

confidence: 99%

Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals

Dey

Brothag

Vijayaraghavan

2019

Front. Cell Dev. Biol.

View full text Add to dashboard Cite

In mammals, motility and fertilizing ability of spermatozoa develop during their passage through the epididymis. After ejaculation, sperm undergo capacitation and hyperactivation in the female reproductive tract-a motility transition that is required for sperm penetration of the egg. Both epididymal initiation of sperm motility and hyperactivation are essential for male fertility. Motility initiation in the epididymis and sperm hyperactivation involve changes in metabolism, cAMP (cyclic adenosine monophosphate), calcium and pH acting through protein kinases and phosphatases. Despite this knowledge, we still do not understand, in biochemical terms, how sperm acquire motility in the epididymis and how motility is altered in the female reproductive tract. Recent data show that the sperm specific protein phosphatase PP1γ2, glycogen synthase kinase 3 (GSK3), and the calcium regulated phosphatase calcineurin (PP2B), are involved in epididymal sperm maturation. The protein phosphatase PP1γ2 is present only in testis and sperm in mammals. PP1γ2 has a isoform-specific requirement for normal function of mammalian sperm. Sperm PP1γ2 is regulated by three proteinsinhibitor 2, inhibitor 3 and SDS22. Changes in phosphorylation of these three inhibitors and their binding to PP1γ2 are involved in initiation and activation of sperm motility. The inhibitors are phosphorylated by protein kinases, one of which is GSK3. The isoform GSK3α is essential for epididymal sperm maturation and fertility. Calcium levels dramatically decrease during sperm maturation and initiation of motility suggesting that the calcium activated sperm phosphatase (PP2B) activity also decreases. Loss of PP2B results in male infertility due to impaired sperm maturation in the epididymis. Thus the three signaling enzymes PP1γ2, GSK3, and PP2B along with the documented PKA (protein kinase A) have key roles in sperm maturation and hyperactivation. Significantly, all these four signaling enzymes are present as specific isoforms only in placental mammals, a testimony to their essential roles in the unique aspects of sperm function in mammals. These findings should lead to a better biochemical understanding of the basis of male infertility and should lead to novel approaches to a male contraception and managed reproduction.

show abstract

PPP1CC2 can form a kinase/phosphatase complex with the testis-specific proteins TSSK1 and TSKS in the mouse testis

Cited by 15 publications

References 41 publications

Boar seminal plasma exosomes maintain sperm function by infiltrating into the sperm membrane

Boar seminal plasma exosomes maintain sperm function by infiltrating into the sperm membrane

Testis-specific serine kinase protein family in male fertility and as targets for non-hormonal male contraception†

Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals

Contact Info

Product

Resources

About