The IP₃ receptor-KRAP complex at the desmosomes: A new player in the apoptotic process

The IP₃ receptor (IP₃R) is a ubiquitously expressed Ca²⁺-release channel located in the endoplasmic reticulum (ER). Ca²⁺ signals originating from the IP₃R initiate or regulate a plethora of cellular events, including cell life and death processes, e.g. exaggerated Ca²⁺ release from the ER to the mitochondria is a trigger for apoptosis. Recently, Cho et al. (Current Biology, 2024, DOI: 10.1016/j.cub.2024.08.057) demonstrated that in epithelial monolayers a sustained [Ca²⁺] elevation caused by the IP₃Rs is responsible for the extrusion of adjacent apoptotic cells out of the epithelial monolayer. Interestingly, the IP₃Rs involved are associated with the desmosomes via K-Ras-induced actin-interacting protein (KRAP). This study not only highlight a novel role of the IP₃R in apoptosis, but also shed a new light on how KRAP -and by extension KRAP-related proteins- contribute to the regulation of IP₃R activity and, more broadly, underscores the crucial role of associated proteins in determining the function of IP₃Rs.