Calmodulin-dependent protein kinase II triggers mouse egg activation and embryo development in the absence of Ca2+ oscillations.
Fertilization in mammalian eggs is accompanied by oscillatory changes in intracellular Ca(2+) concentration, which are critical for initiating and completing egg activation events and the developmental program. Ca(2+)/Camodulin-dependent protein kinase II (CaMKII) is a multifunctional enzyme that is postulated to be the downstream transducer of the Ca(2+) signal in many cell types. We tested the hypothesis that CaMKII is the major integrator of Ca(2+)-induced egg activation events and embryo development by microinjecting a cRNA that encodes a constitutively active (Ca(2+)-independent) mutant form of CaMKII (CA-CaMKII) into mouse eggs. Expression of this cRNA, which does not increase intracellular Ca(2+), induced a sustained rise in CaMKII activity and triggered egg activation events, including cell cycle resumption, and degradation and recruitment of maternal mRNAs; cortical granule exocytosis, however, did not occur normally. Furthermore, when mouse eggs were injected with sperm devoid of Ca(2+)-releasing activity and activated with either CA-CaMKII cRNA or by SrCl(2), similar rates and incidence of development to the blastocyst stage were observed. These results strongly suggest that CaMKII is a major integrator of the Ca(2+) changes that occur following fertilization.
Knott
Jason G
JG
Center for Research on Reproduction and Women's Health, University of Pennsylvania, Philadelphia, PA 19104, USA.
Gardner
Allison J
AJ
Madgwick
Suzanne
S
Jones
Keith T
KT
Williams
Carmen J
CJ
Schultz
Richard M
RM
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000502:physiology; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000502:physiology*; D047108:Embryonic Development / Q000502:physiology*; D005260:Female; D005306:Fertilization / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010063:Ovum / Q000201:enzymology* / Q000378:metabolism; D020554:Sperm Injections, Intracytoplasmic; D013084:Sperm-Ovum Interactions / Q000502:physiology; D013094:Spermatozoa / Q000502:physiology; D046509:Tissue Culture Techniques
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium