A Role for Sperm Surface Protein Disulfide Isomerase Activity in Gamete Fusion: Evidence for the Participation of ERp57

Ellerman, Diego; Myles, Diana G.; Primàkoff, Paul

doi:10.1016/j.devcel.2006.03.011

Cited by 138 publications

(136 citation statements)

References 29 publications

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“…2J) and continued its expression in developing spermatids (Fig. 2K), which is consistent with previous results (Ohtani et al 1993, Ellerman et al 2006.…”

Section: Discussionsupporting

confidence: 92%

“…Blocking GRp58 with antibodies significantly inhibited human sperm from penetrating zona-free hamster oocytes in a dosedependent manner. Different inhibitors of PDI activity were able to inhibit sperm-egg fusion in vitro (Ellerman et al 2006). However, little is known regarding the protein substrates of GRp58 or the mechanism by which it can regulate these substrates in the testis.…”

Section: Introductionmentioning

confidence: 99%

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Disulfide isomerase glucose-regulated protein 58 is required for the nuclear localization and degradation of retinoic acid receptor α

Zhu

Santos²,

Kim³

2010

Reproduction

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Retinoic acid receptor a (RARA) is critical for spermatogenesis, as shown by a sterility phenotype observed in Rara knockout mice. RARA is important in both Sertoli and germ cells of the testis. Here, we demonstrate that a disulfide isomerase glucose-regulated protein 58 (GRp58) participates in the nuclear import and degradation of RARA in Sertoli cells. GRp58 interacted with RARA in the presence of all-trans retinoic acid (ATRA) ligand and, as a complex, it was translocated from the cytoplasm to the nucleus and, then with time, GRp58 dissociated from RARA and was found in the cytoplasm. The GRp58 RNAi treatment disrupted ATRA-dependent RARA nuclear localization, indicating the requirement of GRp58 for RARA nuclear localization. Moreover, treatment with sulfhydryl-modifying agents that oxidize SH-groups of cysteine residues to disulfide bonds abolished ATRA-mediated RARA nuclear localization, suggesting that the thiol oxidoreductase activity of GRp58 may be required for RARA nuclear import. Additionally, the proteasome inhibitor treatment resulted in the co-localization of GRp58 and RARA at the endoplasmic reticulum (ER), suggesting that GRp58 may bring RARA to the ER for the ER-associated degradation (ERAD) of RARA before it is de-coupled from RARA for recycling. In this regard, proteasome inhibitor treatment also increased the interaction of RARA with UBE2J2, an ERAD-associated ubiquitin E2 enzyme. Collectively, the results indicate that GRp58 may act as a molecular chaperone that alters the protein conformation of RARA for its delivery to the nucleus and, then with time, accompanies RARA to the ER for RARA ubiquitination and proteasome-mediated ERAD.

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“…2J) and continued its expression in developing spermatids (Fig. 2K), which is consistent with previous results (Ohtani et al 1993, Ellerman et al 2006.…”

Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Disulfide isomerase glucose-regulated protein 58 is required for the nuclear localization and degradation of retinoic acid receptor α

Zhu

Santos²,

Kim³

2010

Reproduction

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“…An extracellular PDI was shown to be important for gamete fusion in mammals (Ellerman et al, 2006). Analyses of EST databases obtained from egg, sperm, and embryo sac EST libraries in maize (Zea mays) (Engel et al, 2003;Yang et al, 2006) indicated that several PDI-like genes were represented in these libraries.…”

Section: Certain T-dna Insertions In Pdil2-1 Cause Reduced Seed Setmentioning

confidence: 99%

Truncation of a Protein Disulfide Isomerase, PDIL2-1, Delays Embryo Sac Maturation and Disrupts Pollen Tube Guidance inArabidopsis thaliana

et al. 2008

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Pollen tubes must navigate through different female tissues to deliver sperm to the embryo sac for fertilization. Protein disulfide isomerases play important roles in the maturation of secreted or plasma membrane proteins. Here, we show that certain T-DNA insertions in Arabidopsis thaliana PDIL2-1, a protein disulfide isomerase (PDI), have reduced seed set, due to delays in embryo sac maturation. Reciprocal crosses indicate that these mutations acted sporophytically, and aniline blue staining and scanning electron microscopy showed that funicular and micropylar pollen tube guidance were disrupted. A PDIL2-1-yellow fluorescent protein fusion was mainly localized in the endoplasmic reticulum and was expressed in all tissues examined. In ovules, expression in integument tissues was much higher in the micropylar region in later developmental stages, but there was no expression in embryo sacs. We show that reduced seed set occurred when another copy of full-length PDIL2-1 or when enzymatically active truncated versions were expressed, but not when an enzymatically inactive version was expressed, indicating that these T-DNA insertion lines are gain-of-function mutants. Our results suggest that these truncated versions of PDIL2-1 function in sporophytic tissues to affect ovule structure and impede embryo sac development, thereby disrupting pollen tube guidance.

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“…The Cys 120 disulfide bond might have to be reduced to facilitate exposure of the hydrophobic domain. Reduction of disulfide bonds is required to facilitate conformational shifts in several viral fusion proteins and is also essential for mammalian fertilization (37,38). The proposed interaction between hydrophobic regions of Prm1 in one cell and membrane lipids in the opposing plasma membrane can explain why Prm1 only needs to be expressed on one cell of a mating pair to promote fusion (3).…”

Section: Discussionmentioning

confidence: 99%

Prm1 Functions as a Disulfide-linked Complex in Yeast Mating

Olmo

Grote

2010

Journal of Biological Chemistry

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Prm1 is a pheromone-induced membrane glycoprotein that promotes plasma membrane fusion in yeast mating pairs. HAPrm1 migrates at twice its expected molecular weight on nonreducing SDS-PAGE gels and coprecipitates with Prm1-TAP, indicating that Prm1 is a disulfide-linked homodimer. The N terminus of a plasma membrane-localized GFP-Prm1 endocytic mutant projects into the cytoplasm, where it is protected from low pH quenching in live cells and from external protease in spheroplasts. In a revised topological map, Prm1 has four transmembrane domains and two large extracellular loops. Mutation of all four cysteines in the extracellular loops blocked disulfide bond formation and destabilized the Prm1 homodimer without preventing Prm1 transport to contact sites in mating pairs. Cys 120 in loop 1 and Cys 545 in loop 2 form disulfide cross-links in the Prm1 homodimer and are required for fusion activity. Cys 120 lies between a hydrophobic segment formerly thought to be a transmembrane domain and an amphipathic helix. An interaction between either of these regions and the opposing membrane could promote fusion.

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A Role for Sperm Surface Protein Disulfide Isomerase Activity in Gamete Fusion: Evidence for the Participation of ERp57

Cited by 138 publications

References 29 publications

Disulfide isomerase glucose-regulated protein 58 is required for the nuclear localization and degradation of retinoic acid receptor α

Disulfide isomerase glucose-regulated protein 58 is required for the nuclear localization and degradation of retinoic acid receptor α

Truncation of a Protein Disulfide Isomerase, PDIL2-1, Delays Embryo Sac Maturation and Disrupts Pollen Tube Guidance inArabidopsis thaliana

Prm1 Functions as a Disulfide-linked Complex in Yeast Mating

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