The γ isoform of CaM kinase II controls mouse egg activation by regulating cell cycle resumption
نویسندگان
چکیده
Fertilization triggers a rise in intracellular Ca concentration ([Ca]i) in the egg that initiates a series of events known as egg activation. These events include cortical granule exocytosis that establishes a block to polyspermy, resumption of meiosis, and recruitment of maternal mRNAs into polysomes for translation. Several calcium-dependent proteins, including calcium/calmodulin-dependent protein kinase II (CaMKII), have been implicated in egg activation. However, the precise role of CaMKII in mediating specific events of egg activationandthe identityof the isoform(s) present inmouseeggshavenot been unequivocally established. Through targeted deletion of the γ isoform of CaMKII, we find that CaMKIIγ is the predominant CaMKII isoform in mouse eggs and that it is essential for egg activation. Although CaMKIIγ−/− eggs exhibit a normal pattern of Ca oscillations after insemination and undergo cortical granule exocytosis, they fail to resumemeiosisortorecruitmaternalmRNAs.Surprisingly, we find that the recruitment of maternal mRNAs does not directly dependonCaMKII, but requireselevated[Ca]i andmetaphase II exit. We conclude that CaMKIIγ specifically controls mouse egg activation by regulating cell cycle resumption.
منابع مشابه
Possible role for Ca(2+) calmodulin-dependent protein kinase II as an effector of the fertilization Ca(2+) signal in mouse oocyte activation.
The present study shows that Ca(2+) calmodulin-dependent protein kinase II (CaM kinase II) is physiologically activated in fertilized mouse oocytes and is involved in the Ca(2+) response pathways that link the fertilization Ca(2+) signal to meiosis resumption and cortical granule (CG) exocytosis. After 10 min of insemination, CaM kinase II activity increased transiently, then peaked at 1 h and ...
متن کاملCalmodulin-dependent protein kinase gamma 3 (CamKIIgamma3) mediates the cell cycle resumption of metaphase II eggs in mouse.
Mature mammalian eggs are ovulated arrested at meiotic metaphase II. Sperm break this arrest by an oscillatory Ca(2+) signal that is necessary and sufficient for the two immediate events of egg activation: cell cycle resumption and cortical granule release. Previous work has suggested that cell cycle resumption, but not cortical granule release, is mediated by calmodulin-dependent protein kinas...
متن کاملCalmodulin-dependent protein kinase II, and not protein kinase C, is sufficient for triggering cell-cycle resumption in mammalian eggs.
Mouse eggs arrest at metaphase II following ovulation and are only triggered to complete meiosis when fertilized. Sperm break the cell-cycle arrest by a long-lasting series of Ca2+ spikes that lead to an activation of the anaphase-promoting complex/cyclosome. The signal transduction pathway is not fully resolved but both protein kinase C (PKC) and calmodulin-dependent protein kinase II (CamKII)...
متن کاملOscillatory Ca2+ dynamics and cell cycle resumption at fertilization in mammals: a modelling approach.
Fertilization in mammals is accompanied by Ca(2+) oscillations in the egg cytoplasm, leading to exit from meiosis and entry into the first embryonic cell cycle. The signal transduction pathway linking these Ca(2+) changes to cell-cycle related kinases has not yet been fully elucidated, but involves activation of calmodulin-dependent kinase II (CaMKII). Here, we develop a computational model to ...
متن کاملMatrine inhibits diethylnitrosamine-induced HCC proliferation in rats through inducing apoptosis via p53, Bax-dependent caspase-3 activation pathway and down-regulating MLCK overexpression
The proliferation of hepatocellular carcinoma (HCC) cells is one of the leading causes of liver cancer mortality in humans. The inhibiting effects of matrine on HCC cell proliferation have been studied, but the mechanism of that inhibition has not been fully elucidated. Since, apoptosis plays an important role in HCC cell proliferation. We examined the apoptosis-inducing effect of matrine on tu...
متن کامل