Inositol trisphosphate is a second messenger that controls many cellular processes by generating internal calcium signals. It operates through receptors whose molecular and physiological properties closely resemble the calcium-mobilizing ryanodine receptors of muscle. This family of intracellular calcium channels displays the regenerative process of calcium-induced calcium release responsible for the complex spatiotemporal patterns of calcium waves and oscillations. Such a dynamic signalling pathway controls many cellular processes, including fertilization, cell growth, transformation, secretion, smooth muscle contraction, sensory perception and neuronal signalling.

Inositol trisphosphate and calcium signalling

The universality of calcium as an intracellular messenger depends on its enormous versatility. Cells have a calcium signalling toolkit with many components that can be mixed and matched to create a wide range of spatial and temporal signals. This versatility is exploited to control processes as diverse as fertilization, proliferation, development, learning and memory, contraction and secretion, and must be accomplished within the context of calcium being highly toxic. Exceeding its normal spatial and temporal boundaries can result in cell death through both necrosis and apoptosis.

The versatility and universality of calcium signalling

The primary function of inositol 1,4,5-trisphosphate (InsP 3 ) is to function as a second messenger to release Ca 2+ from internal stores. Many cell stimuli act on receptors that are coupled to phospholipase C that hydrolyses phosphatidylinosol 4,5-bisphosphate (PIP 2 ) to release InsP 3 to the cytosol. InsP 3 receptors located on the endoplasmic reticulum respond to this elevation of InsP 3 by releasing Ca 2+ , which is often organized into characteristic spatial (elementary events and waves) and temporal (Ca 2+ oscillations) patterns. This InsP 3 /Ca 2+ pathway has been adapted to control processes as diverse as fertilization, proliferation, contraction, cell metabolism, vesicle and fluid secretion, and information processing in neuronal cells.

Inositol Trisphosphate and Calcium Signaling

The inositol 1,4,5-trisphosphate (InsP3) receptors (InsP3Rs) are a family of Ca2+ release channels localized predominately in the endoplasmic reticulum of all cell types. They function to release Ca2+ into the cytoplasm in response to InsP3 produced by diverse stimuli, generating complex local and global Ca2+ signals that regulate numerous cell physiological processes ranging from gene transcription to secretion to learning and memory. The InsP3R is a calcium-selective cation channel whose gating is regulated not only by InsP3, but by other ligands as well, in particular cytoplasmic Ca2+. Over the last decade, detailed quantitative studies of InsP3R channel function and its regulation by ligands and interacting proteins have provided new insights into a remarkable richness of channel regulation and of the structural aspects that underlie signal transduction and permeation. Here, we focus on these developments and review and synthesize the literature regarding the structure and single-channel properties of the InsP3R.

/pdf/inositol-trisphosphate-receptor-ca2-release-channels-2x1i7h6bsg.pdf

Inositol Trisphosphate Receptor Ca2+ Release Channels

Upon fertilisation by sperm, mammalian eggs are activated by a series of intracellular Ca2+ oscillations that are essential for embryo development. The mechanism by which sperm induces this complex signalling phenomenon is unknown. One proposal is that the sperm introduces an exclusive cytosolic factor into the egg that elicits serial Ca2+ release. The ‘sperm factor’ hypothesis has not been ratified because a sperm-specific protein that generates repetitive Ca2+ transients and egg activation has not been found. We identify a novel, sperm-specific phospholipase C, PLCζ, that triggers Ca2+ oscillations in mouse eggs indistinguishable from those at fertilisation. PLCζ removal from sperm extracts abolishes Ca2+ release in eggs. Moreover, the PLCζ content of a single sperm was sufficient to produce Ca2+ oscillations as well as normal embryo development to blastocyst. Our results are consistent with sperm PLCζ as the molecular trigger for development of a fertilised egg into an embryo.

PLC zeta: a sperm-specific trigger of Ca(2+) oscillations in eggs and embryo development.

Essential role of the inositol 1,4,5-trisphosphate receptor/Ca2+ release channel in Ca2+ waves and Ca2+ oscillations at fertilization of mammalian eggs.

The concentration of cytoplasmic free calcium (Ca2+) increases in various stimulated cells in a wave (Ca2+ wave) and in periodic transients (Ca2+ oscillations). These phenomena are explained by inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release (IICR) and Ca(2+)-induced Ca2+ release (CICR) from separate intracellular stores, but decisive evidence is lacking. A monoclonal antibody to the IP3 receptor inhibited both IICR and CICR upon injection of IP3 and Ca2+ into hamster eggs, respectively. The antibody completely blocked sperm-induced Ca2+ waves and Ca2+ oscillations. The results indicate that Ca2+ release in fertilized hamster eggs is mediated solely by the IP3 receptor, and Ca(2+)-sensitized IICR, but not CICR, generates Ca2+ waves and Ca2+ oscillations.

https://science.sciencemag.org/content/sci/257/5067/251.full.pdf

Block of Ca2+ wave and Ca2+ oscillation by antibody to the inositol 1,4,5-trisphosphate receptor in fertilized hamster eggs.

Development of Inositol Trisphosphate-Induced Calcium Release Mechanism during Maturation of Hamster Oocytes

https://febs.onlinelibrary.wiley.com/doi/pdf/10.1016/0014-5793%2892%2981090-9

Ken Nakada

Papers

Essential role of the inositol 1,4,5-trisphosphate receptor/Ca2+ release channel in Ca2+ waves and Ca2+ oscillations at fertilization of mammalian eggs.

Block of Ca2+ wave and Ca2+ oscillation by antibody to the inositol 1,4,5-trisphosphate receptor in fertilized hamster eggs.

Development of Inositol Trisphosphate-Induced Calcium Release Mechanism during Maturation of Hamster Oocytes

Antibody to the inositol trisphosphate receptor blocks thimerosalenhanced Ca2+‐induced Ca2+ release and Ca2+ oscillations in hamster eggs

Evidence that metalloendoproteases are involved in gamete fusion of Ciona intestinalis, ascidia