Opposing Signals Working Together

Abstract

Fertilization of the vertebrate eggs elicits a transient increase in the intracellular Ca 2+ concentration, thereby releasing the egg from cell cycle arrest in the second meiotic metaphase (see Jessus and Haccard). Two research groups--Mochida and Hunt and Nishiyama et al .--now show that, in addition to the known role of Ca 2+ -calmodulin-dependent protein kinase II (CaMKII), the calcium-dependent phosphatase calcineurin is crucial to this process. In Xenopus egg extracts, calcineurin was transiently activated in response to Ca 2+ independently of CaMKII. Its inhibition affected various Ca 2+ -dependent biochemical and morphological phenomena associated with activation, including cyclin destruction, dephosphorylation of phosphoproteins dephosphorylated at the metaphase-interphase transition, decondensation of sperm chromatin, and the formation of a nuclear envelope. Nishiyama et al . found that a constitutively active form of calcineurin attenuated the formation of sperm asters and inhibited the migration toward each other of male and female pronuclei in fertilized eggs. Mochida and Hunt found that Ca 2+ elicited a second wave of noncalcineurin-mediated phosphatase activity after the initial transient increase in calcineurin activity, which shut down with the next entry into mitosis in "cycling" extract from activated eggs and reappeared when mitosis was complete. Thus, both studies indicate that the Ca 2+ signal in fertilization independently activates calcineurin, as well as CaMKII, and that these two opposing signals work together to break metaphase arrest, allow the cell cycle to proceed, and initiate embryonic development. S. Mochida, T. Hunt, Calcineurin is required to release Xenopus egg extracts from meiotic M phase. Nature 449 , 336-340 (2007). [PubMed] T. Nishiyama, N. Yoshizaki, T. Kishimoto, K. Ohsumi, Transient activation of calcineurin is essential to initiate embryonic development in Xenopus laevis . Nature 449 , 341-345 (2007). [PubMed] C. Jessus, O. Haccard, Calcium's double punch. Nature 449 , 297-298 (2007). [PubMed]