TMEM225: A possible protein phosphatase 1γ2 (PP1γ2) regulator localizes to the equatorial segment in mouse spermatozoa

Matsuura, Minami; Yogo, Keiichiro

doi:10.1002/mrd.22453

Cited by 9 publications

(12 citation statements)

References 43 publications

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“…Isolation of total RNA from various mouse tissues and the reverse transcription reaction was carried out using ISOGEN (Nippon gene) and ReverTra Ace (TOYOBO) as previously described43. For genotyping analysis, genomic DNA was isolated from the tail tip using standard phenol/chloroform extraction.…”

Section: Methodsmentioning

confidence: 99%

A critical role of solute carrier 22a14 in sperm motility and male fertility in mice

Maruyama

Ito

Ikami

et al. 2016

Sci Rep

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We previously identified solute carrier 22a14 (Slc22a14) as a spermatogenesis-associated transmembrane protein in mice. Although Slc22a14 is a member of the organic anion/cation transporter family, its expression profile and physiological role have not been elucidated. Here, we show that Slc22a14 is crucial for sperm motility and male fertility in mice. Slc22a14 is expressed specifically in male germ cells, and mice lacking the Slc22a14 gene show severe male infertility. Although the overall differentiation of sperm was normal, Slc22a14−/− cauda epididymal spermatozoa showed reduced motility with abnormal flagellar bending. Further, the ability to migrate into the female reproductive tract and fertilise the oocyte were also impaired in Slc22a14−/− spermatozoa. The abnormal flagellar bending was thought to be partly caused by osmotic cell swelling since osmotic challenge or membrane permeabilisation treatment alleviated the tail abnormality. In addition, we found structural abnormalities in Slc22a14−/− sperm cells: the annulus, a ring-like structure at the mid-piece–principal piece junction, was disorganised, and expression and localisation of septin 4, an annulus component protein that is essential for the annulus formation, was also impaired. Taken together, our results demonstrated that Slc22a14 plays a pivotal role in normal flagellar structure, motility and fertility in mouse spermatozoa.

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Section: Methodsmentioning

confidence: 99%

A critical role of solute carrier 22a14 in sperm motility and male fertility in mice

Maruyama

Ito

Ikami

et al. 2016

Sci Rep

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“…A decline in PP1γ2 activity occurs during epididymal sperm maturation, due to a decrease in its catalytic activity. Other laboratories have shown that the phosphatase inhibitors also promote hyperactivated sperm motility and acrosome reaction (Furuya et al, 1992a,b;Signorelli et al, 2013;Rotfeld et al, 2014;Matsuura and Yogo, 2015;Tsirulnikov et al, 2019). The enzyme PP1γ2 is present in spermatozoa of a wide range of mammalian species including human and non-human primates (Chakrabarti et al, 2007a;Vijayaraghavan et al, 2007).…”

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.

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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.

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“…The supernatant was transferred to microtubes, mixed with an equal volume of 2× sample buffer (125 mM Tris/SDS (pH 6.8), 4% (w/v) SDS, 20% (v/v) glycerol, 10% (v/v) 2-mercaptoethanol, and 0.002% (w/v) bromophenol blue), and incubated at 100°C for 5 min. In the analysis of transmembrane protein 225 (TMEM225) expression, TMEM225 was immunoprecipitated from testis lysate (300 μg protein) with anti-TMEM225 antibody (Matsuura & Yogo 2015) and resuspended in 2× sample buffer. Sperm were incubated in TYH medium, washed with PBS, and resuspended in 2× sample buffer.…”

Section: Western Blottingmentioning

confidence: 99%

Dysregulation of intracellular pH is a cause of impaired capacitation in Slc22a14-deficient mice

et al. 2022

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Solute carrier 22a member 14 (SLC22A14) plays a critical role in male infertility in mice. We previously revealed that one of the causes of infertility is impaired capacitation. However, the molecular mechanism remained unclear. Here, we show that the influx of HCO3–, a trigger of capacitation, is impaired and intracellular pH is decreased in the sperm of Slc22a14 knockout (KO) mice. While intracellular cAMP concentration did not increase during capacitation in Slc22a14 KO spermatozoa, HCO3–-dependent soluble adenylate cyclase activity was normal, and the addition of 8-bromo cAMP rescued the decreased protein tyrosine phosphorylation. In addition, the intracellular pH of Slc22a14 KO sperm was lower than that of wild-type sperm and did not increase after the addition of HCO3–. Although its relationship to the regulation of intracellular pH is unknown, TMEM225, a possible protein phosphatase inhibitor, was found to be decreased in Slc22a14 KO sperm. The decreased in vitro fertilization rate of Slc22a14 KO sperm was partially rescued by an increase in the intracellular pH (pHi) and the addition of 8-bromo cAMP. These results suggest that SLC22A14 is involved in capacitation through the regulation of HCO3– transport and pHi.

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TMEM225: A possible protein phosphatase 1γ2 (PP1γ2) regulator localizes to the equatorial segment in mouse spermatozoa

Cited by 9 publications

References 43 publications

A critical role of solute carrier 22a14 in sperm motility and male fertility in mice

A critical role of solute carrier 22a14 in sperm motility and male fertility in mice

Signaling Enzymes Required for Sperm Maturation and Fertilization in Mammals

Dysregulation of intracellular pH is a cause of impaired capacitation in Slc22a14-deficient mice

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