title: Specificity of calcium/calmodulin-dependent protein kinases in mouse egg activation.
abstract: CaMKIIγ, the predominant CaMKII isoform in mouse eggs, controls egg activation by regulating cell cycle resumption. In this study we further characterize the involvement and specificity of CaMKIIγ in mouse egg activation. Using exogenous expression of different cRNAs in Camk2g(-/-) eggs, we show that the other multifunctional CaM kinases, CaMKI, and CaMKIV, are not capable of substituting CaMKIIγ to initiate cell cycle resumption in response to a rise in intracellular Ca (2+). Exogenous expression of Camk2g or Camk2d results in activation of nearly 80% of Camk2g(-/-) MII eggs after stimulation with SrCl 2, which does not differ from the incidence of activation of wild-type eggs expressing exogenous Egfp. In contrast, none of the Camk2g(-/-) MII eggs expressing Camk1 or Camk4 activate in response to SrCl 2 treatment. Expression of a constitutively active form of Camk4 (ca-Camk4), but not Camk1, triggers egg activation. EMI2, an APC/C repressor, is a key component in regulating egg activation downstream of CaMKII in both Xenopus laevis and mouse. We show that exogenous expression of either Camk2g, Camk2d, or ca-Camk4, but not Camk1, Camk4, or a catalytically inactive mutant form of CaMKIIγ (kinase-dead) in Camk2g(-/-) mouse eggs leads to almost complete degradation (~90%) of exogenously expressed EMI2 followed by cell cycle resumption. Thus, degradation of EMI2 following its phosphorylation specifically by CaMKII is mechanistically linked to and promotes cell cycle resumption in MII eggs.
authors.affiliation: Department of Biology; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Sergey
authors.initials: S
authors.lastname: Medvedev
authors.affiliation: Department of Biology; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Paula
authors.initials: P
authors.lastname: Stein
authors.affiliation: Department of Biology; University of Pennsylvania; Philadelphia, PA USA.
authors.forename: Richard M
authors.initials: RM
authors.lastname: Schultz
mesh_terms: D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2 / Q000235:genetics / Q000378:metabolism; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D002453:Cell Cycle; D044783:F-Box Proteins / Q000378:metabolism; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D010063:Ovum / Q000166:cytology / Q000378:metabolism*; D010766:Phosphorylation
chemical_list: D044783:F-Box Proteins; C533792:FBXO43 protein, human; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases
keywords: Ca2+ signaling; CaMKII; EMI2; egg activation; meiosis