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IP3, a small molecule with a powerful message
- Source :
- Vrije Universiteit Brussel
- Publication Year :
- 2012
-
Abstract
- Research conducted over the past two decades has provided convincing evidence that cell death, and more specifically apoptosis, can exceed single cell boundaries and can be strongly influenced by intercellular communication networks. We recently reported that gap junctions (i.e. channels directly connecting the cytoplasm of neighboring cells) composed of connexin43 or connexin26 provide a direct pathway to promote and expand cell death, and that inositol 1,4,5-trisphosphate (IP3) diffusion via these channels is crucial to provoke apoptosis in adjacent healthy cells. However, IP3 itself is not sufficient to induce cell death and additional factors appear to be necessary to create conditions in which IP3 will exert proapoptotic effects. Although IP3-evoked Ca2+ signaling is known to be required for normal cell survival, it is also actively involved in apoptosis induction and progression. As such, it is evident that an accurate fine-tuning of this signaling mechanism is crucial for normal cell physiology, while a malfunction can lead to cell death. Here, we review the role of IP3 as an intracellular and intercellular cell death messenger, focusing on the endoplasmic reticulum-mitochondrial synapse, followed by a discussion of plausible elements that can convert IP3 from a physiological molecule to a killer substance. Finally, we highlight several pathological conditions in which anomalous intercellular IP3/Ca2+ signaling might play a role. This article is part of a Special Issue entitled:12th European Symposium on Calcium.
- Subjects :
- Cell death
Programmed cell death
Cell signaling
hemichannel
Gap junction
Cell
Cell Communication
Inositol 1,4,5-Trisphosphate
Biology
Connexin
Connexins
medicine
Animals
Humans
Inositol 1,4,5-Trisphosphate Receptors
Calcium Signaling
Molecular Biology
apoptosis
Cell Biology
Cell biology
Connexin 26
Intercellular communication
medicine.anatomical_structure
Mitochondrial permeability transition pore
Apoptosis
Cytoplasm
Calcium
Signal transduction
Intracellular
Signal Transduction
Subjects
Details
- ISSN :
- 00063002
- Volume :
- 1833
- Issue :
- 7
- Database :
- OpenAIRE
- Journal :
- Biochimica et biophysica acta
- Accession number :
- edsair.doi.dedup.....fbb261504684208503151090cde8a5e8