Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation

Takuya Wakai, Veerle Vanderheyden, Sook Young Yoon, Banyoon Cheon, Nan Zhang, Jan B. Parys, Rafael A. Fissore

Research output: Contribution to journalArticlepeer-review

32 Citations (Scopus)


At the time of fertilization, an increase in the intracellular Ca 2+ concentration ([Ca 2+] i) underlies egg activation and initiation of development in all species studied to date. The inositol 1,4,5-trisphosphate receptor (IP 3R1), which is mostly located in the endoplasmic reticulum (ER) mediates the majority of this Ca 2+ release. The sensitivity of IP 3R1, that is, its Ca 2+ releasing capability, is increased during oocyte maturation so that the optimum [Ca 2+] i response concurs with fertilization, which in mammals occurs at metaphase of second meiosis. Multiple IP 3R1 modifications affect its sensitivity, including phosphorylation, sub-cellular localization, and ER Ca 2+ concentration ([Ca 2+] ER). Here, we evaluated using mouse oocytes how each of these factors affected IP 3R1 sensitivity. The capacity for IP 3-induced Ca 2+ release markedly increased at the germinal vesicle breakdown stage, although oocytes only acquire the ability to initiate fertilization-like oscillations at later stages of maturation. The increase in IP 3R1 sensitivity was underpinned by an increase in [Ca 2+] ER and receptor phosphorylation(s) but not by changes in IP 3R1 cellular distribution, as inhibition of the former factors reduced Ca 2+ release, whereas inhibition of the latter had no impact. Therefore, the results suggest that the regulation of [Ca 2+] ER and IP 3R1 phosphorylation during maturation enhance IP 3R1 sensitivity rendering oocytes competent to initiate oscillations at the expected time of fertilization. The temporal discrepancy between the initiation of changes in IP 3R1 sensitivity and acquisition of mature oscillatory capacity suggest that other mechanisms that regulate Ca 2+ homeostasis also shape the pattern of oscillations in mammalian eggs.

Original languageEnglish
Pages (from-to)705-717
Number of pages13
JournalJournal of cellular physiology
Issue number2
Publication statusPublished - Jan 2012
Externally publishedYes

ASJC Scopus subject areas

  • Physiology
  • Clinical Biochemistry
  • Cell Biology


Dive into the research topics of 'Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation'. Together they form a unique fingerprint.

Cite this