title: IP3, a small molecule with a powerful message.
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 Ca(2+) 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/Ca(2+) signaling might play a role. This article is part of a Special Issue entitled:12th European Symposium on Calcium.
authors.affiliation: Department of Basic Medical Sciences, Ghent University, Ghent, Belgium.
authors.forename: Elke
authors.initials: E
authors.lastname: Decrock
authors.forename: Marijke
authors.initials: M
authors.lastname: De Bock
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.forename: Ashish K
authors.initials: AK
authors.lastname: Gadicherla
authors.forename: Mélissa
authors.initials: M
authors.lastname: Bol
authors.forename: Tinneke
authors.initials: T
authors.lastname: Delvaeye
authors.forename: Peter
authors.initials: P
authors.lastname: Vandenabeele
authors.forename: Mathieu
authors.initials: M
authors.lastname: Vinken
authors.forename: Geert
authors.initials: G
authors.lastname: Bultynck
authors.forename: Dmitri V
authors.initials: DV
authors.lastname: Krysko
authors.forename: Luc
authors.initials: L
authors.lastname: Leybaert
mesh_terms: D000818:Animals; D020013:Calcium Signaling / Q000502:physiology*; D002450:Cell Communication; D000072259:Connexin 26; D017630:Connexins; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism*; D015398:Signal Transduction
chemical_list: D017630:Connexins; C000607042:GJB2 protein, human; D053496:Inositol 1,4,5-Trisphosphate Receptors; D000072259:Connexin 26; D015544:Inositol 1,4,5-Trisphosphate