Bernhardt, Miranda L.;
Stein, Paula;
Carvacho, Ingrid;
Krapp, Christopher;
Ardestani, Goli;
Mehregan, Aujan;
Umbach, David M.;
Bartolomei, Marisa S.;
Fissore, Rafael A.;
Williams, Carmen J.
TRPM7 and CaV3.2 channels mediate Ca2+ influx required for egg activation at fertilization
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Media type:
E-Article
Title:
TRPM7 and CaV3.2 channels mediate Ca2+ influx required for egg activation at fertilization
Contributor:
Bernhardt, Miranda L.;
Stein, Paula;
Carvacho, Ingrid;
Krapp, Christopher;
Ardestani, Goli;
Mehregan, Aujan;
Umbach, David M.;
Bartolomei, Marisa S.;
Fissore, Rafael A.;
Williams, Carmen J.
imprint:
National Academy of Sciences, 2018
Published in:Proceedings of the National Academy of Sciences of the United States of America
Language:
English
ISSN:
0027-8424;
1091-6490
Origination:
Footnote:
Description:
<p>The success of mammalian development following fertilization depends on a series of transient increases in egg cytoplasmic Ca<sup>2+</sup>, referred to as Ca<sup>2+</sup> oscillations. Maintenance of these oscillations requires Ca<sup>2+</sup> influx across the plasma membrane, which is mediated in part by T-type, Ca<sub>V</sub>3.2 channels. Here we show using genetic mouse models that TRPM7 channels are required to support this Ca<sup>2+</sup> influx. Eggs lacking both TRPM7 and Ca<sub>V</sub>3.2 stop oscillating prematurely, indicating that together they are responsible for the majority of Ca<sup>2+</sup> influx immediately following fertilization. Fertilized eggs lacking both channels also frequently display delayed resumption of Ca<sup>2+</sup> oscillations, which appears to require sperm–egg fusion. TRPM7 and Ca<sub>V</sub>3.2 channels almost completely account for Ca<sup>2+</sup> influx observed following store depletion, a process previously attributed to canonical store-operated Ca<sup>2+</sup> entry mediated by STIM/ORAI interactions. TRPM7 serves as a membrane sensor of extracellular Mg<sup>2+</sup> and Ca<sup>2+</sup> concentrations and mediates the effects of these ions on Ca<sup>2+</sup> oscillation frequency. When bred to wild-type males, female mice carrying eggs lacking TRPM7 and Ca<sub>V</sub>3.2 are subfertile, and their offspring have increased variance in postnatal weight. These in vivo findings confirm previous observations linking in vitro experimental alterations in Ca<sup>2+</sup> oscillatory patterns with developmental potential and offspring growth. The identification of TRPM7 and Ca<sub>V</sub>3.2 as key mediators of Ca<sup>2+</sup> influx following fertilization provides a mechanistic basis for the rational design of culture media that optimize developmental potential in research animals, domestic animals, and humans.</p>