title: Regulation of inositol 1,4,5-trisphosphate receptor function during mouse oocyte maturation.
abstract: 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(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.
authors.affiliation: Department of Veterinary and Animal Sciences, University of Massachusetts, Amherst, Massachusetts 01003, USA.
authors.forename: Takuya
authors.initials: T
authors.lastname: Wakai
authors.forename: Veerle
authors.initials: V
authors.lastname: Vanderheyden
authors.forename: Sook-Young
authors.initials: SY
authors.lastname: Yoon
authors.forename: Banyoon
authors.initials: B
authors.lastname: Cheon
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.forename: Jan B
authors.initials: JB
authors.lastname: Parys
authors.forename: Rafael A
authors.initials: RA
authors.lastname: Fissore
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology; D050756:Cyclin-Dependent Kinase Inhibitor Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D009865:Oocytes / Q000166:cytology* / Q000502:physiology*; D010766:Phosphorylation; D021381:Protein Transport
chemical_list: D050756:Cyclin-Dependent Kinase Inhibitor Proteins; D053496:Inositol 1,4,5-Trisphosphate Receptors; C025389:Itpr1 protein, mouse