哺乳類受精におけるCa²⁺シグナリングと細胞周期の制御

抄録

Late Professor Susumu Hagiwara (1922-89) is a great physiologist who discovered Ca²⁺-dependent action potentials in barnacle muscle fibers in 1964, distinct from Hodgkin/Huxley-type Na⁺ spikes. Thereafter, he characterized Ca²⁺ and other ion channels in a wide variety of cells in relation to functions. He was interested in Ca²⁺-regulated cell functions. Fertilization is one of such phenomena. A dramatic increase in intracellular Ca²⁺ occurs at fertilization in eggs of all species examined to date, and it is a pivotal signal for egg activation seen in resumption of meiosis and cell cycle progression. Ca²⁺ signaling at fertilization was first investigated in sea urchin and fish eggs in mid-70s. We began to address the mechanism in mammals in 1980. Mammalian eggs exhibit repetitive Ca²⁺ increase mainly due to Ca²⁺ release from the ER via type 1 IP₃ receptor/Ca²⁺ channel. Accumulated evidence indicates that a cytosolic sperm factor is driven into the ooplasm upon sperm-egg fusion and induces repetitive Ca²⁺ release. Recent studies have shown that a novel isozyme of phospholipase C, PLCζ, is a strong candidate of the sperm factor. Fertilization-like Ca²⁺ oscillations are induced by injection of sperm extract, PLCζ RNA, or recombinant PLCζ into mouse eggs. PLCζ has extremely high Ca²⁺-sensitivity in PLC activity and nuclear translocation ability. These properties qualify PLCζ as the sperm factor that initiates and drives cell cycle-dependent Ca²⁺ oscillations. Ca²⁺ activates CaMK II and thereby ubiquitin/proteasome system, leading to degradation of cyclin, inactivation of metaphase promoting factor, and resumption of meiosis. [J Physiol Sci. 2006;56 Suppl:S4]