Kinase-dependent regulation of inositol 1,4,5-trisphosphate-dependent Ca2+ release during oocyte maturation.
Fertilization induces a species-specific Ca(2+) transient with specialized spatial and temporal dynamics, which are essential to temporally encode egg activation events such as the block to polyspermy and resumption of meiosis. Eggs acquire the competence to produce the fertilization-specific Ca(2+) transient during oocyte maturation, which encompasses dramatic potentiation of inositol 1,4,5-trisphosphate (IP(3))-dependent Ca(2+) release. Here we show that increased IP(3) receptor (IP(3)R) sensitivity is initiated at the germinal vesicle breakdown stage of maturation, which correlates with maturation promoting factor (MPF) activation. Extensive phosphopeptide mapping of the IP(3)R resulted in approximately 70% coverage and identified three residues, Thr-931, Thr-1136, and Ser-114, which are specifically phosphorylated during maturation. Phospho-specific antibody analyses show that Thr-1136 phosphorylation requires MPF activation. Activation of either MPF or the mitogen-activated protein kinase cascade independently, functionally sensitizes IP(3)-dependent Ca(2+) release. Collectively, these data argue that the kinase cascades driving meiotic maturation potentiates IP(3)-dependent Ca(2+) release, possibly trough direct phosphorylation of the IP(3)R.
Sun
Lu
L
Department of Physiology and Biophysics, University of Arkansas for Medical Science, Little Rock, Arkansas 72205, USA.
Haun
Shirley
S
Jones
Richard C
RC
Edmondson
Ricky D
RD
Machaca
Khaled
K
D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling; D002417:Cattle; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000032:analysis* / Q000378:metabolism*; D016200:Maturation-Promoting Factor / Q000378:metabolism*; D000090204:Mesothelin; D051379:Mice; D008969:Molecular Sequence Data; D009865:Oocytes / Q000166:cytology / Q000378:metabolism*; D009866:Oogenesis; D010748:Phosphopeptides / Q000032:analysis; D010766:Phosphorylation; D010770:Phosphotransferases / Q000378:metabolism; D016415:Sequence Alignment; D014981:Xenopus / Q000502:physiology*
D053496:Inositol 1,4,5-Trisphosphate Receptors; C000715528:Msln protein, mouse; D010748:Phosphopeptides; D015544:Inositol 1,4,5-Trisphosphate; D010770:Phosphotransferases; D016200:Maturation-Promoting Factor; D000090204:Mesothelin; D002118:Calcium