Calcium signaling differentiation during Xenopus oocyte maturation

Abstract

Ca(2+) is the universal signal for egg activation at fertilization in all sexually reproducing species. The Ca(2+) signal at fertilization is necessary for egg activation and exhibits specialized spatial and temporal dynamics. Eggs acquire the ability to produce the fertilization-specific Ca(2+) signal during oocyte maturation. However, the mechanisms regulating Ca(2+) signaling differentiation during oocyte maturation remain largely unknown. At fertilization, Xenopus eggs produce a cytoplasmic Ca(2+) (Ca(2+)(cyt)) rise that lasts for several minutes, and is required for egg activation. Here, we show that during oocyte maturation Ca(2+) transport effectors are tightly modulated. The plasma membrane Ca(2+) ATPase (PMCA) is completely internalized during maturation, and is therefore unable to extrude Ca(2+) out of the cell. Furthermore, IP(3)-dependent Ca(2+) release is required for the sustained Ca(2+)(cyt) rise in eggs, showing that Ca(2+) that is pumped into the ER leaks back out through IP(3) receptors. This apparent futile cycle allows eggs to maintain elevated cytoplasmic Ca(2+) despite the limited available Ca(2+) in intracellular stores. Therefore, Ca(2+) signaling differentiates in a highly orchestrated fashion during Xenopus oocyte maturation endowing the egg with the capacity to produce a sustained Ca(2+)(cyt) transient at fertilization, which defines the egg's competence to activate and initiate embryonic development.

Ca2+ signaling differentiation during oocyte maturation

“…In fact, this biphasic Ca 2þ response is replicated by Ca 2þ mobilizing agents, such as IP 3 (Fig. 2) or Ca 2þ ionophore, indicating that it is an inherent property of the Ca 2þ signaling machinery in eggs (El Jouni et al, 2005). A similar Ca 2þ mobilizing trigger (IP 3 ) produces a significantly smaller, more transient Ca 2þ response in oocytes (Fig.…”

“…There is also a tendency for increased Ca 2þ store content during maturation, but its contribution to the enhanced Ca 2þ release in eggs appear to be small (Jones et al, 1994;Mehlmann and Kline, 1994;Jellerette et al, 2004;El Jouni et al, 2005).…”

“…The Ca 2þ wave is followed by a sustained Ca 2þ plateau that lasts for several minutes (Busa and Nuccitelli, 1985;El Jouni et al, 2005). The Ca 2þ wave is due to Ca 2þ release from intracellular stores through the IP 3 receptor (IP 3 R), since it is inhibited by blocking IP 3 -dependent Ca 2þ release or PIP2 hydrolysis (Larabell and Nuccitelli, 1992;Nuccitelli et al, 1993;Runft et al, 1999).…”

“…The contribution of different pathways to Ca 2þ signaling in Xenopus eggs has been analyzed, leading to the conclusion that the most critical determinants of Ca 2þ signaling dynamics in eggs are increased affinity of the IP 3 R and inhibition of Ca 2þ extrusion (Machaca, 2004;El Jouni et al, 2005). Injection of sub-threshold levels of IP 3 produces no response (on average) in oocytes, but lead to Ca 2þ release in eggs (Machaca, 2004).…”

“…SREs are rare in eggs as the threshold for inducing them occurs over a small window of IP 3 concentrations, due to increased IP 3 R affinity (Machaca, 2004). This functional clustering of elementary Ca 2þ release events is almost certainly due to physical clustering of IP 3 receptors during maturation as observed by immunofluorescence (Parys et al, 1994;Kume et al, 1997;Machaca, 2004;El Jouni et al, 2005). In Xenopus oocytes Ca 2þ puffs are thought to be due to the opening of small cluster of 10-20 channels (Parker et al, 1996).…”