ALBERT

Description: Apoptosis in most cell types is accompanied by altered Ca 2+ homeostasis. During apoptosis, caspase-3 mediated cleavage of the type 1 inositol 1,4,5-trisphosphate receptor (IP 3 R1) generates a 95-kDa C-terminal fragment (C-IP 3 R1), which represents the channel domain of the receptor. Aged mouse eggs display abnormal Ca 2+ homeostasis and express C-IP 3 R1, although whether or not C-IP 3 R1 expression contributes to Ca 2+ misregulation or a decrease in developmental competency is unknown. We sought to answer these questions by injecting in mouse oocytes and eggs cRNAs encoding C-IP 3 R1. We found that: (1) expression of C-IP 3 R1 in eggs lowered the Ca 2+ content of the endoplasmic reticulum (ER), although, as C-IP 3 R1 is quickly degraded at this stage, its expression did not impair pre-implantation embryo development; (2) expression of C-IP 3 R1 in eggs enhanced fragmentation associated with aging; (3) endogenous IP 3 R1 is required for aging associated apoptosis, as its down-regulation prevented fragmentation, and expression of C-IP 3 R1 in eggs with downregulated IP 3 R1 partly restored fragmentation; (4) C-IP 3 R1 expression in GV oocytes resulted in persistent levels of protein, which abolished the increase in the ER releasable Ca 2+ pool that occurs during maturation, undermined the Ca 2+ oscillatory ability of matured eggs and their activation potential. Collectively, this study supports a role for IP 3 R1 and C-IP 3 R1 in regulating Ca 2+ homeostasis and the ER Ca 2+ content during oocyte maturation. Nevertheless, the role of C-IP 3 R1 on Ca 2+ homeostasis in aged eggs seems minor, as in MII eggs the majority of endogenous IP 3 R1 remains intact and C-IP 3 R1 undergoes rapid turnover. J. Cell. Physiol. © 2014 Wiley Periodicals, Inc.