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Published online 5 April 2004. doi:10.1083/jcb.200309138
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 165, Number 1, 63-75
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Article

 Ca2+cyt negatively regulates the initiation of oocyte maturation

Lu Sun and Khaled Machaca

Department of Physiology and Biophysics, University of Arkansas for Medical Sciences, Little Rock, AR 72205

Address correspondence to Khaled Machaca, Dept. of Physiology and Biophysics, University of Arkansas for Medical Sciences, 4301 West Markham St., Slot 505, Little Rock, AR 72205. Tel.: (501) 603-1596. Fax: (501) 686-8167. email: kamachaca{at}uams.edu

Ca2+ is a ubiquitous intracellular messenger that is important for cell cycle progression. Genetic and biochemical evidence support a role for Ca2+ in mitosis. In contrast, there has been a long-standing debate as to whether Ca2+ signals are required for oocyte meiosis. Here, we show that cytoplasmic Ca2+ (Ca2+cyt) plays a dual role during Xenopus oocyte maturation. Ca2+ signals are dispensable for meiosis entry (germinal vesicle breakdown and chromosome condensation), but are required for the completion of meiosis I. Interestingly, in the absence of Ca2+cyt signals oocytes enter meiosis more rapidly due to faster activation of the MAPK-maturation promoting factor (MPF) kinase cascade. This Ca2+-dependent negative regulation of the cell cycle machinery (MAPK-MPF cascade) is due to Ca2+cyt acting downstream of protein kinase A but upstream of Mos (a MAPK kinase kinase). Therefore, high Ca2+cyt delays meiosis entry by negatively regulating the initiation of the MAPK-MPF cascade. These results show that Ca2+ modulates both the cell cycle machinery and nuclear maturation during meiosis.

Key Words: calcium; meiosis; cell cycle; meiotic maturation; Xenopus

Abbreviations used in this paper: BAPTA, 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; CA2+cyt, cytoplasmic Ca2+; F-Ca, Ca2+-free Ringer; GVBD, germinal vesicle breakdown; H-Ca, high Ca2+; ICa,Cl, Ca2+-activated Cl– currents; L-Ca, low Ca2+; MPF, maturation promoting factor; N-Ca, normal Ca2+; NEBD, nuclear envelope breakdown; PKI, PKA inhibitor; SOCE, store-operated Ca2+ entry.


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