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Ca2+ oscillations promote APC/C-dependent cyclin B1 degradation during metaphase arrest and completion of meiosis in fertilizing mouse eggs

Lookup NU author(s): Dr Victoria Nixon, Dr Mark Levasseur, Dr Alexander McDougall, Professor Keith Jones

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Abstract

Cyclin 131, the regulatory component of M phase-promoting factor (MPF), is degraded during the metaphase-anaphase transition in an anaphase-promoting complex/cyclosome (APC/C)-dependent process [1]. MPF activity is stable in eggs, and a sperm-triggered Ca2+ signal is needed to promote cyclin degradation [2]. In frogs, a single Ca2+ spike promotes cell cycle resumption, but, in mammals, the Ca2+ signal is more complex, consisting of a series of spikes that stop several hours after sperm fusion [3]. Using dual imaging in mouse eggs, we have examined how the Ca2+ signal generates cyclin B1 destruction using destructible and nondestructible GFP-tagged constructs. APC/ C activity was present in unfertilized eggs, giving cyclin B1 a half-life of 1.15 +/- 0.28 hr. However, APC/C-dependent cyclin degradation was elevated 6-fold when sperm raised cytosolic Ca2+ levels above 600 nM. This activation was transitory since cyclin B1 levels recovered between Ca2+ spikes. For continued cyclin degradation at basal Ca2+ levels, multiple spikes were needed. APC/C-mediated degradation was observed until eggs had completed meiosis with the formation of pronuclei, and, at this time, Call spikes stopped. Therefore, the physiological need for a repetitive Ca2+ signal in mammals is to ensure long-term cyclin destruction during a protracted exit from meiosis.


Publication metadata

Author(s): Nixon VL; Jones KT; McDougall A; Levasseur M

Publication type: Article

Publication status: Published

Journal: Current Biology

Year: 2002

Volume: 12

Issue: 9

Pages: 746-750

ISSN (print): 0960-9822

ISSN (electronic): 1879-0445

Publisher: Cell Press

URL: http://dx.doi.org/10.1016/S0960-9822(02)00811-4

DOI: 10.1016/S0960-9822(02)00811-4


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