02891nas a2200325   4500008004100000245009700041210006900138260001300207300001100220490000800231520180900239653001202048653002202060653004702082653001102129653003102140653004302171653000902214653001202223653002002235653002202255100001802277700002502295700002102320700001902341700001502360700001802375700002302393856014902416       2012                        eng d00aRegulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation.0 aRegulation of inositol 145trisphosphate receptor function during  c2012 Feb  a705-170 v2273 aAt 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(3)R1), which is mostly located in the endoplasmic reticulum (ER) mediates the majority of this Ca(2+) release. The sensitivity of IP(3)R1, 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(3)R1 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(3)R1 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(3)R1 sensitivity was underpinned by an increase in [Ca(2+)](ER) and receptor phosphorylation(s) but not by changes in IP(3)R1 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(3)R1 phosphorylation during maturation enhance IP(3)R1 sensitivity rendering oocytes competent to initiate oscillations at the expected time of fertilization. The temporal discrepancy between the initiation of changes in IP(3)R1 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.10aAnimals10aCalcium Signaling10aCyclin-Dependent Kinase Inhibitor Proteins10aFemale10aGene Expression Regulation10aInositol 1,4,5-Trisphosphate Receptors10aMice10aOocytes10aPhosphorylation10aProtein Transport1 aWakai, Takuya1 aVanderheyden, Veerle1 aYoon, Sook-Young1 aCheon, Banyoon1 aZhang, Nan1 aParys, Jan, B1 aFissore, Rafael, A  uhttps://www.umass.edu/veterinary-animal-sciences/research-faculty/publications/regulation-of-inositol-145-trisphosphate-receptor-function-during