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

Abstract

Fertilization of a mammalian egg induces a series of ‘zinc sparks’ that are necessary for inducing the egg-to-embryo transition. Despite the importance of these zinc efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches to resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy dispersive spectroscopy, X-ray fluorescence microscopy, and 3D elemental tomography for high resolution elemental mapping. Here we show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each of which contains, on average, 106 zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. We conclude that the discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes.

Authors:
 [1];  [2];  [3];  [3];  [4];  [4];  [4];  [5];  [6];  [7];  [8];  [9]
  1. Northwestern Univ., Evanston, IL (United States). Chemistry of Life Processes Inst.
  2. Northwestern Univ., Evanston, IL (United States). Chemistry of Life Processes Inst.; Northwestern Univ., Evanston, IL (United States). Atomic and Nanoscale Characterization Experimental Center
  3. Northwestern Univ., Evanston, IL (United States). Dept. of Obstetrics and Gynecology
  4. Argonne National Lab. (ANL), Argonne, IL (United States). X-ray Science Division
  5. Northwestern Univ., Evanston, IL (United States). Chemistry of Life Processes Inst.; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry
  6. Northwestern Univ., Evanston, IL (United States). Chemistry of Life Processes Inst.; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry
  7. Northwestern Univ., Evanston, IL (United States). Atomic and Nanoscale Characterization Experimental Center; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Northwestern Univ., Evanston, IL (United States). Dept. of Materials Science and Engineering
  8. Northwestern Univ., Evanston, IL (United States). Chemistry of Life Processes Inst.; Northwestern Univ., Evanston, IL (United States). Dept. of Obstetrics and Gynecology; Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences
  9. Northwestern Univ., Evanston, IL (United States). Chemistry of Life Processes Inst.; Northwestern Univ., Evanston, IL (United States). Dept. of Chemistry; Northwestern Univ., Evanston, IL (United States). Dept. of Molecular Biosciences
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States)
Sponsoring Org.:
W.M. Keck Foundation; Chicago Biomedical Consortium; National Institutes of Health (NIH); USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22)
OSTI Identifier:
1248232
Grant/Contract Number:  
AC02-06CH11357; P01 HD021921; GM38784; U54HD076188; T32GM105
Resource Type:
Accepted Manuscript
Journal Name:
Nature Chemistry
Additional Journal Information:
Journal Volume: 7; Journal Issue: 2; Journal ID: ISSN 1755-4330
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; 47 OTHER INSTRUMENTATION

Citation Formats

Que, Emily L., Bleher, Reiner, Duncan, Francesca E., Kong, Betty Y., Gleber, Sophie C., Vogt, Stefan, Chen, Si, Garwin, Seth A., Bayer, Amanda R., Dravid, Vinayak P., Woodruff, Teresa K., and O'Halloran, Thomas V. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks. United States: N. p., 2014. Web. doi:10.1038/NCHEM.2133.
Que, Emily L., Bleher, Reiner, Duncan, Francesca E., Kong, Betty Y., Gleber, Sophie C., Vogt, Stefan, Chen, Si, Garwin, Seth A., Bayer, Amanda R., Dravid, Vinayak P., Woodruff, Teresa K., & O'Halloran, Thomas V. Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks. United States. doi:10.1038/NCHEM.2133.
Que, Emily L., Bleher, Reiner, Duncan, Francesca E., Kong, Betty Y., Gleber, Sophie C., Vogt, Stefan, Chen, Si, Garwin, Seth A., Bayer, Amanda R., Dravid, Vinayak P., Woodruff, Teresa K., and O'Halloran, Thomas V. Mon . "Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks". United States. doi:10.1038/NCHEM.2133. https://www.osti.gov/servlets/purl/1248232.
@article{osti_1248232,
title = {Quantitative mapping of zinc fluxes in the mammalian egg reveals the origin of fertilization-induced zinc sparks},
author = {Que, Emily L. and Bleher, Reiner and Duncan, Francesca E. and Kong, Betty Y. and Gleber, Sophie C. and Vogt, Stefan and Chen, Si and Garwin, Seth A. and Bayer, Amanda R. and Dravid, Vinayak P. and Woodruff, Teresa K. and O'Halloran, Thomas V.},
abstractNote = {Fertilization of a mammalian egg induces a series of ‘zinc sparks’ that are necessary for inducing the egg-to-embryo transition. Despite the importance of these zinc efflux events little is known about their origin. To understand the molecular mechanism of the zinc spark we combined four physical approaches to resolve zinc distributions in single cells: a chemical probe for dynamic live-cell fluorescence imaging and a combination of scanning transmission electron microscopy with energy dispersive spectroscopy, X-ray fluorescence microscopy, and 3D elemental tomography for high resolution elemental mapping. Here we show that the zinc spark arises from a system of thousands of zinc-loaded vesicles, each of which contains, on average, 106 zinc atoms. These vesicles undergo dynamic movement during oocyte maturation and exocytosis at the time of fertilization. We conclude that the discovery of these vesicles and the demonstration that zinc sparks originate from them provides a quantitative framework for understanding how zinc fluxes regulate cellular processes.},
doi = {10.1038/NCHEM.2133},
journal = {Nature Chemistry},
number = 2,
volume = 7,
place = {United States},
year = {2014},
month = {12}
}

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Works referenced in this record:

The Galvanization of Biology: A Growing Appreciation for the Roles of Zinc
journal, February 1996


Transition metals in control of gene expression
journal, August 1993


Zinc Biochemistry: From a Single Zinc Enzyme to a Key Element of Life
journal, January 2013


Zinc availability regulates exit from meiosis in maturing mammalian oocytes
journal, August 2010

  • Kim, Alison M.; Vogt, Stefan; O'Halloran, Thomas V.
  • Nature Chemical Biology, Vol. 6, Issue 9
  • DOI: 10.1038/nchembio.419

Zinc Sparks Are Triggered by Fertilization and Facilitate Cell Cycle Resumption in Mammalian Eggs
journal, April 2011

  • Kim, Alison M.; Bernhardt, Miranda L.; Kong, Betty Y.
  • ACS Chemical Biology, Vol. 6, Issue 7
  • DOI: 10.1021/cb200084y

Zinc Requirement During Meiosis I–Meiosis II Transition in Mouse Oocytes Is Independent of the MOS-MAPK Pathway1
journal, March 2011


A Zinc-Dependent Mechanism Regulates Meiotic Progression in Mammalian Oocytes1
journal, April 2012


Zinc Maintains Prophase I Arrest in Mouse Oocytes Through Regulation of the MOS-MAPK Pathway1
journal, July 2012


Full-term mouse development by abolishing Zn2+-dependent metaphase II arrest without Ca2+ release
journal, June 2010

  • Suzuki, T.; Yoshida, N.; Suzuki, E.
  • Development, Vol. 137, Issue 16
  • DOI: 10.1242/dev.049791

Zinc Depletion Causes Multiple Defects in Ovarian Function during the Periovulatory Period in Mice
journal, February 2012


Mouse Emi2 as a distinctive regulatory hub in second meiotic metaphase
journal, August 2010

  • Suzuki, T.; Suzuki, E.; Yoshida, N.
  • Development, Vol. 137, Issue 19
  • DOI: 10.1242/dev.052480

Maternally-derived zinc transporters ZIP6 and ZIP10 drive the mammalian oocyte-to-egg transition
journal, August 2014

  • Kong, B. Y.; Duncan, F. E.; Que, E. L.
  • MHR: Basic science of reproductive medicine, Vol. 20, Issue 11
  • DOI: 10.1093/molehr/gau066

Structure and Function of Voltage-Gated Ion Channels
journal, June 1995


Mammalian Zinc Transport, Trafficking, and Signals
journal, June 2006

  • Cousins, Robert J.; Liuzzi, Juan P.; Lichten, Louis A.
  • Journal of Biological Chemistry, Vol. 281, Issue 34
  • DOI: 10.1074/jbc.R600011200

Biology, structure and mechanism of P-type ATPases
journal, April 2004

  • Kühlbrandt, Werner
  • Nature Reviews Molecular Cell Biology, Vol. 5, Issue 4
  • DOI: 10.1038/nrm1354

Identification and Cloning of a  -Cell-Specific Zinc Transporter, ZnT-8, Localized Into Insulin Secretory Granules
journal, August 2004


Importance of Zinc in the Central Nervous System: The Zinc-Containing Neuron
journal, May 2000

  • Frederickson, Christopher J.; Suh, Sang Won; Silva, David
  • The Journal of Nutrition, Vol. 130, Issue 5
  • DOI: 10.1093/jn/130.5.1471S

ZnT-3, a putative transporter of zinc into synaptic vesicles
journal, December 1996

  • Palmiter, R. D.; Cole, T. B.; Quaife, C. J.
  • Proceedings of the National Academy of Sciences, Vol. 93, Issue 25
  • DOI: 10.1073/pnas.93.25.14934

Zinc is a novel intracellular second messenger
journal, May 2007

  • Yamasaki, Satoru; Sakata-Sogawa, Kumiko; Hasegawa, Aiko
  • The Journal of Cell Biology, Vol. 177, Issue 4
  • DOI: 10.1083/jcb.200702081

Video image analysis of labile zinc in viable pancreatic islet cells using a specific fluorescent probe for zinc.
journal, July 1994

  • Zalewski, P. D.; Millard, S. H.; Forbes, I. J.
  • Journal of Histochemistry & Cytochemistry, Vol. 42, Issue 7
  • DOI: 10.1177/42.7.8014471

Design and application of genetically encoded biosensors
journal, March 2011


Metals in Neurobiology: Probing Their Chemistry and Biology with Molecular Imaging
journal, May 2008

  • Que, Emily L.; Domaille, Dylan W.; Chang, Christopher J.
  • Chemical Reviews, Vol. 108, Issue 5
  • DOI: 10.1021/cr078203u

Imaging mobile zinc in biology
journal, April 2010


Aqueous Coordination Chemistry of Quinoline-Based Fluorescence Probes for the Biological Chemistry of Zinc
journal, December 1999

  • Fahrni, Christoph J.; O'Halloran, Thomas V.
  • Journal of the American Chemical Society, Vol. 121, Issue 49
  • DOI: 10.1021/ja992709f

Problems with the application of quin-2-AM to measuring cytoplasmic free calcium in plant cells
journal, March 1986


A Scalable Synthesis of Meso-Substituted Dipyrromethanes
journal, November 2003

  • Laha, Joydev K.; Dhanalekshmi, Savithri; Taniguchi, Masahiko
  • Organic Process Research & Development, Vol. 7, Issue 6
  • DOI: 10.1021/op034083q

Visualizing Ascorbate-Triggered Release of Labile Copper within Living Cells using a Ratiometric Fluorescent Sensor
journal, February 2010

  • Domaille, Dylan W.; Zeng, Li; Chang, Christopher J.
  • Journal of the American Chemical Society, Vol. 132, Issue 4
  • DOI: 10.1021/ja907778b

Influence of Coordination Geometry upon Copper(II/I) Redox Potentials. Physical Parameters for Twelve Copper Tripodal Ligand Complexes
journal, September 1999

  • Ambundo, Edna A.; Deydier, Marie-Veronique; Grall, Andrew J.
  • Inorganic Chemistry, Vol. 38, Issue 19
  • DOI: 10.1021/ic990334t

Role of Zinc during Hamster Sperm Capacitation1
journal, December 1994


Autometallographic demonstration of zinc ions in rat sperm cells
journal, September 1997


Use of a zinc fluorophore to measure labile pools of zinc in body fluids and cell-conditioned media
journal, April 2006

  • Zalewski, Peter; Truong-Tran, Ai; Lincoln, Stephen
  • BioTechniques, Vol. 40, Issue 4
  • DOI: 10.2144/06404RR02

Femtomolar Sensitivity of Metalloregulatory Proteins Controlling Zinc Homeostasis
journal, June 2001


Synthetic fluorescent probes for monovalent copper
journal, August 2013


Detection and Imaging of Zinc Secretion from Pancreatic β-Cells Using a New Fluorescent Zinc Indicator
journal, February 2002

  • Gee, Kyle R.; Zhou, Zhang-Lin; Qian, Wei-Jun
  • Journal of the American Chemical Society, Vol. 124, Issue 5
  • DOI: 10.1021/ja011774y

ZP4, an Improved Neuronal Zn 2+ Sensor of the Zinpyr Family
journal, February 2003

  • Burdette, Shawn C.; Frederickson, Christopher J.; Bu, Weiming
  • Journal of the American Chemical Society, Vol. 125, Issue 7
  • DOI: 10.1021/ja0287377

Quantitative studies of changes in cortical granule number and distribution in the mouse oocyte during meiotic maturation
journal, November 1988


Ovastacin, a cortical granule protease, cleaves ZP2 in the zona pellucida to prevent polyspermy
journal, April 2012

  • Burkart, Anna D.; Xiong, Bo; Baibakov, Boris
  • The Journal of Cell Biology, Vol. 197, Issue 1
  • DOI: 10.1083/jcb.201112094

Dynamics of cortical granule exocytosis at fertilization in living mouse eggs
journal, May 1996


Diffusible ion localization by ion microscopy: a comparison of chemically prepared and fast-frozen, freeze-dried, unfixed liver sections
journal, April 1980


Immersion Autometallography: Histochemical In Situ Capturing of Zinc Ions in Catalytic Zinc-Sulfur Nanocrystals
journal, December 2004

  • Danscher, Gorm; Stoltenberg, Meredin; Bruhn, Mikkel
  • Journal of Histochemistry & Cytochemistry, Vol. 52, Issue 12
  • DOI: 10.1369/jhc.4A6371.2004

Aqueous Solubilities, Solubility Products and Standard Oxidation-Reduction Potentials of the Metal Sulfides
journal, January 1988

  • Licht, Stuart
  • Journal of The Electrochemical Society, Vol. 135, Issue 12
  • DOI: 10.1149/1.2095471

The Bionanoprobe: hard X-ray fluorescence nanoprobe with cryogenic capabilities
journal, December 2013


Alignment of low-dose X-ray fluorescence tomography images using differential phase contrast
journal, December 2013

  • Hong, Young Pyo; Gleber, Sophie-Charlotte; O'Halloran, Thomas V.
  • Journal of Synchrotron Radiation, Vol. 21, Issue 1
  • DOI: 10.1107/S1600577513029512

New Developments in Hard X-ray Fluorescence Microscopy for In-situ Investigations of Trace Element Distributions in Aqueous Systems of Soil Colloids
journal, October 2013


Cytoarchitectonic distribution of zinc in the hippocampus of man and the rat
journal, August 1983


Role of zinc trafficking in male fertility: from germ to sperm
journal, April 2014

  • Foresta, Carlo; Garolla, Andrea; Cosci, Ilaria
  • Human Reproduction, Vol. 29, Issue 6
  • DOI: 10.1093/humrep/deu075

The role of Hv1 and CatSper channels in sperm activation: Hv1 and CatSper channels in sperm activation
journal, November 2010


    Works referencing / citing this record:

    Ferti PROTEKT, Oncofertility Consortium and the Danish Fertility-Preservation Networks – What Can We Learn From Their Experiences?
    journal, January 2019

    • von Wolff, Michael; Andersen, Claus Yding; Woodruff, Teresa K.
    • Clinical Medicine Insights: Reproductive Health, Vol. 13
    • DOI: 10.1177/1179558119845865

    A conditional proteomics approach to identify proteins involved in zinc homeostasis
    journal, September 2016

    • Miki, Takayuki; Awa, Masashi; Nishikawa, Yuki
    • Nature Methods, Vol. 13, Issue 11
    • DOI: 10.1038/nmeth.3998

    A Zinc(II) Photocage Based on a Decarboxylation Metal Ion Release Mechanism for Investigating Homeostasis and Biological Signaling
    journal, September 2015

    • Basa, Prem N.; Antala, Sagar; Dempski, Robert E.
    • Angewandte Chemie International Edition, Vol. 54, Issue 44
    • DOI: 10.1002/anie.201505778

    A Zinc(II) Photocage Based on a Decarboxylation Metal Ion Release Mechanism for Investigating Homeostasis and Biological Signaling
    journal, September 2015

    • Basa, Prem N.; Antala, Sagar; Dempski, Robert E.
    • Angewandte Chemie, Vol. 127, Issue 44
    • DOI: 10.1002/ange.201505778

    A conditional proteomics approach to identify proteins involved in zinc homeostasis
    journal, September 2016

    • Miki, Takayuki; Awa, Masashi; Nishikawa, Yuki
    • Nature Methods, Vol. 13, Issue 11
    • DOI: 10.1038/nmeth.3998

    Ferti PROTEKT, Oncofertility Consortium and the Danish Fertility-Preservation Networks – What Can We Learn From Their Experiences?
    journal, January 2019

    • von Wolff, Michael; Andersen, Claus Yding; Woodruff, Teresa K.
    • Clinical Medicine Insights: Reproductive Health, Vol. 13
    • DOI: 10.1177/1179558119845865