Non-Apoptotic Role of Apoptotic Caspases in the Drosophila Nervous System

Abstract

An increasing number of studies demonstrate that cells can activate apoptotic caspases but not die and, instead, display profound changes in cellular structure and function. In this minireview, we will discuss observations in the nervous system of Drosophila melanogaster that illustrate non-apoptotic roles of apoptotic caspases. We will preface these examples with similar observations in other experimental systems and end with a discussion of how apoptotic caspase activity might be constrained to provide non-lethal functions without killing the cell.

Extramacrochaetae regulates Notch signaling in theDrosophilaeye through non-apoptotic caspase activity

“…The effects may depend on the full caspase cascade of initiator and effector caspases, because sensitivity to p35 indicates that caspases other than Dronc are necessary, and because mutating dronc alone gave lesser degrees of rescue than deleting rpr , grim , and hid . This is consistent with many other studies that describe the pathways for apoptotic and non-apoptotic caspase functions as similar(Kanuka et al, 2005; Kuranaga & Miura, 2007; Aram et al, 2017; Nakajima & Kuranaga, 2017; Baena-Lopez et al, 2018; Su, 2020; Colon-Plaza & Su, 2022).…”

“…They are expressed as inactive zymogens that are then activated by signals (initiator caspases) or by cleavage by caspases (effector caspases) in a feed-forward process that is expected to kill cells rapidly once a threshold of caspase activity has been crossed(Fuchs & Steller, 2011). Many studies show that caspases can also mediate non-apoptotic processes, although what differentiates apoptotic from non-apoptotic outcomes is uncertain, as the same caspase cascade of initiator and effector caspases seems to be involved (Yamaguchi & Miura, 2015; Aram, Yacobi-Sharon, & Arama, 2017; Nakajima & Kuranaga, 2017; Baena-Lopez, Arthurton, Xu, & Galasso, 2018; Colon-Plaza & Su, 2022). Non-apoptotic caspase activities are of particular interest because of their contributions to multiple diseases(Su, 2020).…”

“…Caspases can also mediate non-apoptotic processes. What differentiates apoptotic from non-apoptotic outcomes is uncertain, as the same caspase cascade of initiator and effector caspases seems to be involved (Aram et al, 2017;Baena-Lopez et al, 2018;Colon-Plaza and Su, 2022;Kanuka et al, 2005;Kuranaga and Miura, 2007;Nakajima and Kuranaga, 2017;Su, 2020). In ex mutants, the increased diap1 transcription does not affect cell death much but causes an increase in wg signaling activity (Wang and Baker, 2019).…”

Non-apoptotic caspase events and Atf3 expression underlie direct neuronal differentiation of adult neural stem cells

“…In embryonic neurospheres in vitro, blocking these events limits neuronal differentiation and neurite extension (Fernando et al, 2005). Finally, in the embryonic peripheral nervous system in Drosophila, non-apoptotic caspase-mediated cleavage of signaling pathway effectors limit neural progenitor proliferation to control neuronal production (Colon-Plaza and Su, 2022; Kuranaga et al, 2006). Non-apoptotic caspase events involve activation of the direct caspase pathway converging onto the activation of effector Caspases 3 and 7 (activated forms noted as Cas3*, Cas7*) by proteolytic cleavage, but can be tracked using Cas3*/Cas7* sensors.…”

Keeping Cell Death Alive: An Introduction into the French Cell Death Research Network

“…The recent understanding that apoptotic factors have non-canonical roles in various cellular processes [ 7 , 8 , 9 , 10 , 11 ] raised considerable interest in the international scientific community and researchers of the FCDRN. Non-canonical functions of apoptotic proteins, such as cIAPs, Bcl2 family members and caspases have been shown to contribute to cellular differentiation, morphogenesis or the cross-talks between apoptosis and autophagy pathways.…”