Regulation of endoplasmic reticulum Ca2+ oscillations in mammalian eggs

Takuya Wakai, Nan Zhang, Peter Vangheluwe, Rafael A. Fissore

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Changes in the intracellular concentration of free calcium ([Ca2+]i) regulate diverse cellular processes including fertilization. In mammalian eggs, the [Ca2+]i changes induced by the sperm unfold in a pattern of periodical rises, also known as [Ca2+]i oscillations. The source of Ca2+ during oscillations is the endoplasmic reticulum ([Ca2+]ER), but it is presently unknown how [Ca2+]ER is regulated. Here, we show using mouse eggs that [Ca2+]i oscillations induced by a variety of agonists, including PLCf, SrCl2 and thimerosal, provoke simultaneous but opposite changes in [Ca2+]ER and cause differential effects on the refilling and overall load of [Ca2+]ER. We also found that Ca2+ influx is required to refill [Ca2+]ER, because the loss of [Ca2+]ER was accelerated in medium devoid of Ca2+. Pharmacological inactivation of the function of the mitochondria and of the Ca2+-ATPase pumps PMCA and SERCA altered the pattern of oscillations and abruptly reduced [Ca2+]ER, especially after inactivation of mitochondria and SERCA functions. We also examined the expression of SERCA2b protein and found that it was expressed throughout oocyte maturation and attained a conspicuous cortical cluster organization in mature eggs. We show that its overexpression reduces the duration of inositol-1,4,5-trisphosphate-induced [Ca2+]i rises, promotes initiation of oscillations and enhances refilling of [Ca2+]ER. Collectively, our results provide novel insights on the regulation of [Ca2+]ER oscillations, which underlie the unique Ca2+-signalling system that activates the developmental program in mammalian eggs.

Original languageEnglish
Pages (from-to)5714-5724
Number of pages11
JournalJournal of cell science
Volume126
Issue number24
DOIs
Publication statusPublished - Dec 15 2013

Keywords

  • Ca oscillations
  • Egg activation
  • Endoplasmic reticulum
  • Fertilization
  • Oocyte maturation
  • Serca

ASJC Scopus subject areas

  • Cell Biology

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