Dipeptidase-Inactivated tACE Action In Vivo: Selective Inhibition of Sperm-Zona Pellucida Binding in the Mouse1

Deguchi, Eishi; Tani, Taeko; Watanabe, Hidenobu; Yamada, Shuichi; Kondoh, Gen

doi:10.1095/biolreprod.107.060004

Cited by 30 publications

(19 citation statements)

References 36 publications

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“…The male germ-cell-specific variant (tACE) controls ADAM3 distribution on the membrane (6). The GPIase activity of tACE (i.e., the release of glycosylphosphatidylinositol-anchored proteins from the membrane) is implicated in ADAM3 modification during epididymal maturation (32). In addition to tissue-specific factors, recent studies indicated that the ubiquitously expressed proteins, TPST2 (protein-tyrosine sulfotransferase 2) and INPP5B (inositol polyphosphate-5-phosphatase B), are involved in ADAM3 quality control (13,33).…”

Section: Discussionmentioning

confidence: 99%

Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility

Tokuhiro

Ikawa

Benham

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

134

167

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A disintegrin and metalloproteinase 3 (ADAM3) is a sperm membrane protein critical for both sperm migration from the uterus into the oviduct and sperm primary binding to the zona pellucida (ZP). Here we show that the testis-specific protein disulfide isomerase homolog (PDILT) cooperates with the testis-specific calreticulin-like chaperone, calsperin (CALR3), in the endoplasmic reticulum and plays an indispensable role in the disulfide-bond formation and folding of ADAM3. Pdilt −/− mice were male infertile because ADAM3 could not be folded properly and transported to the sperm surface without the PDILT/CALR3 complex. Peculiarly we find that not only Pdilt −/− , but also Adam3 −/− , spermatozoa effectively fertilize eggs when the eggs are surrounded in cumulus oophorus. These findings reveal that ADAM3 requires testis-specific private chaperones to be folded properly and that the principle role of ADAM3 is for sperm migration into the oviduct but not for the fertilization event. Moreover, the importance of primary sperm ZP binding, which has been thought to be a critical step in mammalian fertilization, should be reconsidered.

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Section: Discussionmentioning

confidence: 99%

Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility

Tokuhiro

Ikawa

Benham

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

134

167

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“…Fuchs and colleagues reported that dipeptidase activity of testicular ACE (tACE) is required for sperm-ZP binding (Fuchs et al, 2005). Thereafter, we reported that dipeptidase activity of tACE is functional in the epididymis (Deguchi et al, 2007). In addition, Shum and co-workers have shown that angiotensin II, a product of ACE dipeptidase action, regulates the distribution of proton channels in the epididymal epithelium and contributes to the pH homeostasis of the epididymal fluids (Shum et al, 2008).…”

Section: Egfp(k268q)-gpi Release and Gm1 Relocation Is Associated Wmentioning

confidence: 92%

Mouse sperm undergo GPI-anchored protein release associated with lipid raft reorganization and acrosome reaction to acquire fertility

Watanabe

Kondoh

2011

Journal of Cell Science

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Mammalian sperm undergo several maturation steps after leaving the testis to become competent for fertilization. Important changes occur in sperm within the female reproductive tract, although the molecular mechanisms underlying these processes remain unclear. To investigate sperm membrane remodeling upon sperm maturation, we developed transgenic mouse lines carrying glycosylphosphatidylinositol (GPI)-anchored enhanced green fluorescent protein (EGFP–GPI) and traced the fate of this fluorescent protein during the fertility-acquiring process in sperm in vitro and in vivo. When the GFP-labeled sperm were treated with compounds for promoting the acrosome reaction, EGFP–GPI was released from the sperm surface crosslinked with characteristic relocation of a lipid raft marker ganglioside GM1. Sperm ejaculated into the uterus strongly expressed EGFP–GPI in the head region, whereas a part of the oviductal sperm lost fluorescence in a manner that was dependent on the presence of angiotensin-converting enzyme (ACE). Moreover, sperm on the zona pellucida of eggs in the oviduct were all found to have low levels of GFP. These results suggest that sperm undergoing GPI-anchored protein release associated with reorganization of lipid rafts and the acrosome reaction acquire fertilization potential.

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“…ACE sheds various GPI-anchored proteins from the sperm surface such as TESP5 [ID: T1-175] and , and this function plays a role in fertilization (Kondoh et al, 2005). Transgenic mice carrying a mutant dipeptidase-inactivated tACE are fertile, but sperm-zona pellucida binding is impaired (Deguchi et al, 2007).…”

Section: Flagellar Proteins and Abnormalities Associatedmentioning

confidence: 99%

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

Hermo¹,

Pelletier²,

Cyr³

et al. 2009

Microscopy Res & Technique

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Spermiogenesis constitutes the steps involved in the metamorphosis of spermatids into spermatozoa. It involves modification of several organelles in addition to the formation of several structures including the flagellum and cytoplasmic droplet. The flagellum is composed of a neck region and middle, principal, and end pieces. The axoneme composed of nine outer microtubular doublets circularly arranged to form a cylinder around a central pair of microtubules is present throughout the flagellum. The middle and principal pieces each contain specific components such as the mitochondrial sheath and fibrous sheath, respectively, while outer dense fibers are common to both. A plethora of proteins are constituents of each of these structures, with each playing key roles in functions related to the fertility of spermatozoa. At the end of spermiogenesis, a portion of spermatid cytoplasm remains associated with the released spermatozoa, referred to as the cytoplasmic droplet. The latter has as its main feature Golgi saccules, which appear to modify the plasma membrane of spermatozoa as they move down the epididymal duct and hence may be partly involved in male gamete maturation. The end product of spermatogenesis is highly streamlined and motile spermatozoa having a condensed nucleus equipped with an acrosome. Spermatozoa move through the female reproductive tract and eventually penetrate the zona pellucida and bind to the egg plasma membrane. Many proteins have been implicated in the process of fertilization as well as a plethora of proteins involved in the development of spermatids and sperm, and these are high lighted in this review.

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Dipeptidase-Inactivated tACE Action In Vivo: Selective Inhibition of Sperm-Zona Pellucida Binding in the Mouse1

Cited by 30 publications

References 36 publications

Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility

Protein disulfide isomerase homolog PDILT is required for quality control of sperm membrane protein ADAM3 and male fertility

Mouse sperm undergo GPI-anchored protein release associated with lipid raft reorganization and acrosome reaction to acquire fertility

Surfing the wave, cycle, life history, and genes/proteins expressed by testicular germ cells. Part 3: Developmental changes in spermatid flagellum and cytoplasmic droplet and interaction of sperm with the zona pellucida and egg plasma membrane

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