Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

Que, Emily L.; Bleher, Reiner; Duncan, Francesca E.; Kong, Betty Y.; Gleber, Sophie-Charlotte; Vogt, Stefan; Chen, Si; Garwin, Seth A.; Bayer, Amanda R.; Dravid, Vinayak P.; Woodruff, Teresa K.; O’Halloran, Thomas V.

doi:10.1038/nchem.2133

Cited by 196 publications

(212 citation statements)

References 55 publications

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“…For example, large amounts of zinc are imported and localized in the cortical granules of oocytes during meiotic maturation from the prophase I to the metaphase (211,218,342), which is required for growth arrest after the first meiotic division (211). The accumulated zinc is ejected from the oocyte to decrease bioavailable zinc during egg activation immediately following intracellular calcium oscillations, which is termed the "zinc spark" (211).…”

Section: Zinc Containing Vesicles/granules In Cellsmentioning

confidence: 99%

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Kambe

Tsuji

Hashimoto

et al. 2015

Physiological Reviews

873

797

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Zinc is involved in a variety of biological processes, as a structural, catalytic, and intracellular and intercellular signaling component. Thus zinc homeostasis is tightly controlled at the whole body, tissue, cellular, and subcellular levels by a number of proteins, with zinc transporters being particularly important. In metazoan, two zinc transporter families, Zn transporters (ZnT) and Zrt-, Irt-related proteins (ZIP) function in zinc mobilization of influx, efflux, and compartmentalization/ sequestration across biological membranes. During the last two decades, significant progress has been made in understanding the molecular properties, expression, regulation, and cellular and physiological roles of ZnT and ZIP transporters, which underpin the multifarious functions of zinc. Moreover, growing evidence indicates that malfunctioning zinc homeostasis due to zinc transporter dysfunction results in the onset and progression of a variety of diseases. This review summarizes current progress in our understanding of each ZnT and ZIP transporter from the perspective of zinc physiology and pathogenesis, discussing challenging issues in their structure and zinc transport mechanisms.

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Section: Zinc Containing Vesicles/granules In Cellsmentioning

confidence: 99%

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

Kambe

Tsuji

Hashimoto

et al. 2015

Physiological Reviews

873

797

View full text Add to dashboard Cite

show abstract

“…[4] Free Zn 2+ has been implicated in various signaling pathways, [1] and recently fertilization of oocytes has been shown to trigger "zinc sparks" that serve to initiate meiosis at the beginning stages of embryotic development. [5] The development of new methodologies to simulate fluctuations in Zn 2+ concentrations in a spatiotemporal manner would facilitate the understanding of complex signaling processes.Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201505778. …”

mentioning

confidence: 99%

A Zinc(II) Photocage Based on a Decarboxylation Metal Ion Release Mechanism for Investigating Homeostasis and Biological Signaling

et al. 2015

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Metal ion signaling in biology has been studied extensively with ortho-nitrobenzyl photocages; however, the low quantum yields and other optical properties are not ideal for these applications. We describe the synthesis and characterization of NTAdeCage, the first member in a new class of Zn 2+ photocages that utilizes a light-driven decarboxylation reaction in the metal ion release mechanism. NTAdeCage binds Zn 2+ with sub-pM affinity using a modified nitrilotriacetate chelator and exhibits an almost 6 order of magnitude decrease in metal binding affinity upon uncaging. In contrast to other metal ion photocages, NTAdeCage and the corresponding Zn 2+ complex undergo efficient photolysis with quantum yields approaching 30%. The ability of NTAdeCage to mediate the uptake of 65 Zn 2+ by Xenopus laevis oocytes expressing hZIP4 demonstrates the viability of this photocaging strategy to execute biological assays. Keywords cage compounds; coordination compounds; photolysis; X-ray diffraction; zinc The importance of Zn 2+ beyond structural and catalytic functions in proteins has become increasingly apparent. [1] Zinc and iron regulated proteins (ZIPs) increase cytosolic Zn 2+ concentrations; in contrast, zinc transporter (ZnT) proteins decrease cytosolic Zn 2+ . [2,3] Elucidating the function of free or loosely bound Zn 2+ in the cytosol as well as in intracellular compartments remains important; however, the ability to modulate Zn 2+ levels in vivo in a time-resolved manner remains elusive. [4] Free Zn 2+ has been implicated in various signaling pathways, [1] and recently fertilization of oocytes has been shown to trigger "zinc sparks" that serve to initiate meiosis at the beginning stages of embryotic development. [5] The development of new methodologies to simulate fluctuations in Zn 2+ concentrations in a spatiotemporal manner would facilitate the understanding of complex signaling processes.Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/anie.201505778. HHS Public Access Author Manuscript Author ManuscriptAuthor Manuscript Author ManuscriptThe photochemistry of ortho-nitrobenzyl (oNB) chromophores initially was recognized as a means to deliver Ca 2+ in a controlled manner to biological receptors using light. [6] We subsequently adapted two Ca 2+ -releasing strategies to develop photocaged complexes for biologically relevant metal ions such as Zn 2+ , Cu + and Fe 3+ . [7,8] In the Cast photocages, decreased electron density on a coordinated aniline nitrogen atom following photolysis lowers chelator binding affinity. [9][10][11] While this strategy can adequately buffer Ca 2+ at typical intracellular resting levels (ca. 100 nM) and simulate biologically relevant concentration increases, [6,12] the reliance on weakly coordinating aniline-based ligands precludes use with Zn 2+ , which experiences tighter intracellular homeostasis. [11] Alternatively, photolytically breaking a carbon-heteroatom bond provides compounds that release metal ions through the reduction ...

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“…The twinkling that emanates from her hands as they create snowflakes and Olaf are reminiscent of the billions of zinc sparks that occur when a sperm connects with an egg during a successful egg-to-embryo transition (Que et al 2015). Without gloves, Elsa can procreate, using wind power.…”

Section: Son (Sown) Versus Daughter and Conception Via Whirlwindsmentioning

confidence: 99%

Storm Power, an Icy Tower and Elsa’s Bower: The Winds of Change in Disney’s Frozen

Dundes

Streiff

Streiff³

2018

Social Sciences

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In Disney's box office sensation Frozen (2013), Elsa conjures powers rivaling those of Zeus, which is an echo of the shifting gender dynamics at the time of the film's release. By independently creating offspring Olaf and Marshmallow through whirlwinds, Elsa's parthenogenesis (virgin birth) evokes wind-driven pollination, allowing her to circumvent any male role in creation. However, Elsa's autonomy clashes with the traditional gender hierarchy, which is reinforced by a cultural context replete with latent symbolic meanings. Examples include both carrots and carats as phallic symbols, eggs as representations of the procreative potential that is appropriated by men and devalued in women, gender bias in perceptions of magic and enchantment, and the value of the nubile nymph over the tempestuous termagant. The normalcy of male dominance likely drives the resolution of the plot, in which Elsa learns to wield power in a non-threatening manner. In addition to having implications for gender roles, Frozen also portrays a mélange of gender symbolism through Elsa's snowmen creations, which function as an expression of the storm of controversy surrounding the subversion of binary conceptions of gender. In the end, Frozen serves as a cautionary tale about the dangers inherent in an unattached female as the ultimate potentate. This content analysis suggests that the film reflects fears surrounding the maelstrom of societal changes including expanding fertility options and the re-conceptualization of gender identity-pressing issues likely to sustain Frozen's relevance.

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Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks

Cited by 196 publications

References 55 publications

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

The Physiological, Biochemical, and Molecular Roles of Zinc Transporters in Zinc Homeostasis and Metabolism

A Zinc(II) Photocage Based on a Decarboxylation Metal Ion Release Mechanism for Investigating Homeostasis and Biological Signaling

Storm Power, an Icy Tower and Elsa’s Bower: The Winds of Change in Disney’s Frozen

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