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Store-operated Ca2+ entry is not required for fertilization-induced Ca2+ signaling in mouse eggs.


ABSTRACT: Repetitive oscillations in cytoplasmic Ca2+ due to periodic Ca2+ release from the endoplasmic reticulum (ER) drive mammalian embryo development following fertilization. Influx of extracellular Ca2+ to support the refilling of ER stores is required for sustained Ca2+ oscillations, but the mechanisms underlying this Ca2+ influx are controversial. Although store-operated Ca2+ entry (SOCE) is an appealing candidate mechanism, several groups have arrived at contradictory conclusions regarding the importance of SOCE in oocytes and eggs. To definitively address this question, Ca2+ influx was assessed in oocytes and eggs lacking the major components of SOCE, the ER Ca2+ sensor STIM proteins, and the plasma membrane Ca2+ channel ORAI1. We generated oocyte-specific conditional knockout (cKO) mice for Stim1 and Stim2, and also generated Stim1/2 double cKO mice. Females lacking one or both STIM proteins were fertile and their ovulated eggs displayed normal patterns of Ca2+ oscillations following fertilization. In addition, no impairment was observed in ER Ca2+ stores or Ca2+ influx following store depletion. Similar studies were performed on eggs from mice globally lacking ORAI1; no abnormalities were observed. Furthermore, spontaneous Ca2+ influx was normal in oocytes from Stim1/2 cKO and ORAI1-null mice. Finally, we tested if TRPM7-like channels could support spontaneous Ca2+ influx, and found that it was largely prevented by NS8593, a TRPM7-specific inhibitor. Fertilization-induced Ca2+ oscillations were also impaired by NS8593. Combined, these data robustly show that SOCE is not required to support appropriate Ca2+ signaling in mouse oocytes and eggs, and that TRPM7-like channels may contribute to Ca2+ influx that was previously attributed to SOCE.

SUBMITTER: Bernhardt ML 

PROVIDER: S-EPMC5461193 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature

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Store-operated Ca<sup>2+</sup> entry is not required for fertilization-induced Ca<sup>2+</sup> signaling in mouse eggs.

Bernhardt Miranda L ML   Padilla-Banks Elizabeth E   Stein Paula P   Zhang Yingpei Y   Williams Carmen J CJ  

Cell calcium 20170211


Repetitive oscillations in cytoplasmic Ca<sup>2+</sup> due to periodic Ca<sup>2+</sup> release from the endoplasmic reticulum (ER) drive mammalian embryo development following fertilization. Influx of extracellular Ca<sup>2+</sup> to support the refilling of ER stores is required for sustained Ca<sup>2+</sup> oscillations, but the mechanisms underlying this Ca<sup>2+</sup> influx are controversial. Although store-operated Ca<sup>2+</sup> entry (SOCE) is an appealing candidate mechanism, several  ...[more]

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