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Calcium and connexin-based intercellular communication, a deadly catch?
Elke Decrock1, Mathieu Vinken, Mélissa Bol
1Department of Basic Medical Sciences - Physiology Group, Faculty of Medicine and Health Sciences, Ghent University, B-9000 Ghent, Belgium.
Abstract:
Ca(2+) is known as a universal messenger mediating a wide variety of cellular processes, including cell death. In fact, this ion has been proposed as the 'cell death master', not only at the intracellular but also at the intercellular level. The most direct form of intercellular spread of cell death is mediated by gap junction channels. These channels have been shown to propagate cell death as well as cell survival signals between the cytoplasm of neighbouring cells, reflecting the dual role of Ca(2+) signals, i.e. cell death versus survival. Its precursor, the unopposed hemichannel (half of a gap junction channel), has recently joined in as a toxic pore connecting the intracellular with the extracellular environment and allowing the passage of a range of substances. The biochemical nature of the so-called intercellular cell death molecule, transferred through gap junctions or released/taken up via hemichannels, remains elusive but several studies pinpoint Ca(2+) itself or its messenger inositol trisphosphate as the responsible masters in crime. Although direct evidence is still lacking, indirect data including Ca(2+) involvement in intercellular communication and cell death, and effects of intercellular communication on intracellular Ca(2+) homeostasis, support this hypothesis. In addition, hemichannels and their molecular building blocks, connexin or pannexin proteins, may exert their effects on Ca(2+)-dependent cell death at the intracellular level, independently from their channel functions. This review provides a cutting edge overview of the current knowledge and underscores the intimate connection between intercellular communication, Ca(2+) signalling and cell death.
Insights
Calcium (Ca2+) acts as a cell death messenger, spreading signals between cells via gap junctions. This review explores the link between intercellular communication, Ca2+ signaling, and cell death pathways.
Area of Science:
- Cell Biology
- Biochemistry
- Physiology
Background:
- Calcium ions (Ca2+) are crucial intracellular messengers regulating diverse cellular functions, including cell death.
- Intercellular communication, particularly through gap junction channels, plays a significant role in propagating cell death signals.
- Hemichannels, a component of gap junctions, also contribute to intercellular communication and may influence cell death.
Purpose of the Study:
- To review the current understanding of the connection between intercellular communication and Ca2+ signaling in cell death.
- To explore the role of Ca2+ as a mediator of cell death at both intracellular and intercellular levels.
- To discuss the potential involvement of Ca2+ and its messengers in intercellular cell death signaling.
Main Methods:
- Literature review of studies investigating Ca2+ signaling, gap junctions, hemichannels, and cell death.
- Analysis of evidence supporting the role of Ca2+ in intercellular communication and cell death.
- Examination of the molecular mechanisms underlying Ca2+-dependent cell death mediated by intercellular communication.
Main Results:
- Ca2+ signals can mediate both cell death and cell survival signals between adjacent cells via gap junctions.
- Hemichannels facilitate the passage of substances between intracellular and extracellular environments, potentially contributing to cell death.
- Ca2+ or inositol trisphosphate are implicated as intercellular cell death molecules, though direct evidence is pending.
- Connexin and pannexin proteins, forming hemichannels, may influence Ca2+-dependent cell death independently of channel activity.
Conclusions:
- There is a strong, albeit indirect, link between intercellular communication, Ca2+ signaling, and cell death.
- Ca2+ is a central player in cell death, acting both intracellularly and intercellularly.
- Further research is needed to elucidate the precise mechanisms of Ca2+-mediated intercellular cell death signaling.
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