TY - JOUR
T1 - Regulation of inositol 1,4,5-trisphosphate receptor type 1 function during oocyte maturation by MPM-2 phosphorylation
AU - Vanderheyden, Veerle
AU - Wakai, Takuya
AU - Bultynck, Geert
AU - De Smedt, Humbert
AU - Parys, Jan B.
AU - Fissore, Rafael A.
N1 - Funding Information:
We thank Irène Willems and Changli He for excellent technical assistance. This work was supported by grant R01 HD051872 from the NIH to R.A.F., J.B.P and H.D.S. and by grant GOA/09/012 from the Research Council of the K.U.Leuven to J.B.P and H.D.S. V.V was recipient of a Travel Grant of the Research Foundation-Flanders (FWO).
PY - 2009/7
Y1 - 2009/7
N2 - Egg activation and further embryo development require a sperm-induced intracellular Ca2+ signal at the time of fertilization. Prior to fertilization, the egg's Ca2+ machinery is therefore optimized. To this end, during oocyte maturation, the sensitivity, i.e. the Ca2+ releasing ability, of the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), which is responsible for most of this Ca2+ release, markedly increases. In this study, the recently discovered specific Polo-like kinase (Plk) inhibitor BI2536 was used to investigate the role of Plk1 in this process. BI2536 inactivates Plk1 in oocytes at the early stages of maturation and significantly decreases IP3R1 phosphorylation at an MPM-2 epitope at this stage. Moreover, this decrease in Plk1-dependent MPM-2 phosphorylation significantly lowers IP3R1 sensitivity. Finally, using in vitro phosphorylation techniques we identified T2656 as a major Plk1 site on IP3R1. We therefore propose that the initial increase in IP3R1 sensitivity during oocyte maturation is underpinned by IP3R1 phosphorylation at an MPM-2 epitope(s).
AB - Egg activation and further embryo development require a sperm-induced intracellular Ca2+ signal at the time of fertilization. Prior to fertilization, the egg's Ca2+ machinery is therefore optimized. To this end, during oocyte maturation, the sensitivity, i.e. the Ca2+ releasing ability, of the inositol 1,4,5-trisphosphate receptor type 1 (IP3R1), which is responsible for most of this Ca2+ release, markedly increases. In this study, the recently discovered specific Polo-like kinase (Plk) inhibitor BI2536 was used to investigate the role of Plk1 in this process. BI2536 inactivates Plk1 in oocytes at the early stages of maturation and significantly decreases IP3R1 phosphorylation at an MPM-2 epitope at this stage. Moreover, this decrease in Plk1-dependent MPM-2 phosphorylation significantly lowers IP3R1 sensitivity. Finally, using in vitro phosphorylation techniques we identified T2656 as a major Plk1 site on IP3R1. We therefore propose that the initial increase in IP3R1 sensitivity during oocyte maturation is underpinned by IP3R1 phosphorylation at an MPM-2 epitope(s).
KW - Calcium
KW - IPR
KW - MPM-2 phosphorylation
KW - Mammalian eggs
KW - Oocyte maturation
KW - Plk1
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UR - http://www.scopus.com/inward/citedby.url?scp=67649088035&partnerID=8YFLogxK
U2 - 10.1016/j.ceca.2009.04.004
DO - 10.1016/j.ceca.2009.04.004
M3 - Article
C2 - 19482353
AN - SCOPUS:67649088035
SN - 0143-4160
VL - 46
SP - 56
EP - 64
JO - Cell Calcium
JF - Cell Calcium
IS - 1
ER -