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Review
. 2012 Nov;79(11):742-56.
doi: 10.1002/mrd.22078. Epub 2012 Sep 28.

Calcium signaling in mammalian egg activation and embryo development: the influence of subcellular localization

Yi-Liang Miao  1 , Carmen J Williams
Affiliations
Review

Calcium signaling in mammalian egg activation and embryo development: the influence of subcellular localization

Yi-Liang Miao et al. Mol Reprod Dev. 2012 Nov.

Abstract

Calcium (Ca(2+) ) signals drive the fundamental events surrounding fertilization and the activation of development in all species examined to date. Initial studies of Ca(2+) signaling at fertilization in marine animals were tightly linked to new discoveries of bioluminescent proteins and their use as fluorescent Ca(2+) sensors. Since that time, there has been rapid progress in our understanding of the key functions for Ca(2+) in many cell types and of the impact of cellular localization on Ca(2+) signaling pathways. In this review, which focuses on mammalian egg activation, we consider how Ca(2+) is regulated and stored at different stages of oocyte development and examine the functions of molecules that serve as both regulators of Ca(2+) release and effectors of Ca(2+) signals. We then summarize studies exploring how Ca(2+) directs downstream effectors mediating both egg activation and later signaling events required for successful preimplantation embryo development. Throughout this review, we focus attention on how localization of Ca(2+) signals influences downstream signaling events, and attempt to highlight gaps in our knowledge that are ripe for future research.

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Conflict of interest statement

The authors declare no competing financial interests

Figures

Figure 1
Figure 1. Localization of STIM2 in maturing mouse oocytes
Mouse oocytes at the germinal vesicle (GV), germinal vesicle breakdown (GVBD), metaphase I (MI), and metaphase II (MII) stages were fixed and stained for both STIM2 (red) and calreticulin, an endoplasmic reticulum (ER; green) marker. Antibodies used were anti-STIM2 (Cat# 4125; ProSci Inc., Poway, CA) and anti-calreticulin (cat# sc-7431; Santa Cruz Biotechnology, Santa Cruz, CA). Spindle region indicated on merged images with arrows.
Figure 2
Figure 2. Characteristic appearance of first and second sperm-induced Ca2+ transients
Arrow indicates “shoulder” in first Ca2+ transient.
Figure 3
Figure 3. Ca2+ release and reuptake pathways during initial egg activation
Schematic diagram of Ca2+ release from ER stores in response to PLCζ-mediated generation of IP3 and the channels responsible for Ca2+ extrusion and reuptake. 1) PLCζ hydrolyzes PIP2 in cortical pool to generate IP3 and DAG. 2) IP3 mediates Ca2+ release from ER stores via IP3R1. 3) Increased cytosolic Ca2+ and possibly other signaling molecules activate endogenous egg PLC(s), causing generation of additional IP3. 4) Ca2+ re-enters ER stores via SERCA pumps. 5) Cytoplasmic Ca2+ is extruded from egg by PMCA pumps. 6) DAG and Ca2+ promote plasma membrane translocation of cPKC. 7) Phosphorylation of cPKC-sensitive Ca2+ channels promotes Ca2+ influx. PB I, first polar body; ER, endoplasmic reticulum; PLCζ, phospholipase C zeta; PIP2, phosphatidylinositol 4,5-bisphosphate; IP3, inositol 1,4,5-trisphosphate; DAG, diacylglycerol; ePLC, egg phospholipase C; cPKC, conventional protein kinase C; IP3R1, type 1 IP3 receptor; Ca2+, calcium; SERCA, sarcoplasmic/endoplasmic reticulum Ca2+ ATPase pump; PMCA, plasma membrane Ca2+ ATPase pump; ?, cPKC-sensitive plasma membrane Ca2+ channel(s), identity unknown.
Figure 4
Figure 4. Phospholipase C isoforms
Schematic diagram of functional domains of the six mammalian PLC sub-families. The size ranges of the proteins and their splice forms within each PLC sub-family and known regulatory mechanisms are indicated. Based on 3 distinct microarray datasets deposited in GEO Profiles, mammalian oocytes contain the listed PLC isoforms. Isoforms listed in larger, bold font have the highest signal intensities; isoforms in smaller, plain font have lower signal intensities, suggesting relative abundance of the mRNAs. PLC isoforms with an average signal intensity in fully grown oocytes of < 50 across the three datasets are not listed. RasGEF, guanine nucleotide exchange factor for Ras-like small GTPases domain; PH, pleckstrin homology domain; EF, EF-hand-like domain; X and Y, catalytic domains; C2, C2-domain Ca2+-binding pocket; RA, Ras-association domain; SH2, Src-homology 2 domain; SH3, Src-homology 3 domain; PIP3, phosphatidylinositol 3,4,5-trisphosphate; PA, phosphatidic acid; AA, arachidonic acid; Rac, Rac GTPases.
See this image and copyright information in PMC

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