Projects per year
Abstract
Stress-induced cell death, mainly apoptosis, and its subsequent tissue repair is interlinked although our knowledge of this connection is still very limited. An intriguing finding is apoptosis-induced proliferation (AiP), an evolutionary conserved mechanism employed by apoptotic cells to trigger compensatory proliferation of their neighboring cells. Studies using Drosophila as a model organism have revealed that apoptotic caspases and c-Jun N-terminal kinase (JNK) signaling play critical roles to activate AiP. For example, the initiator caspase Dronc, the caspase-9 ortholog in Drosophila, promotes activation of JNK leading to release of mitogenic signals and AiP. Recent studies further revealed that Dronc relocates to the cell cortex via Myo1D, an unconventional myosin, and stimulates production of reactive oxygen species (ROS) to trigger AiP. During this process, ROS can attract hemocytes, the Drosophila macrophages, which further amplify JNK signaling cell non-autonomously. However, the intrinsic components connecting Dronc, ROS and JNK within the stressed signal-producing cells remain elusive. Here, we identified LIM domain kinase 1 (LIMK1), a kinase promoting cellular F-actin polymerization, as a novel regulator of AiP. F-actin accumulates in a Dronc-dependent manner in response to apoptotic stress. Suppression of F-actin polymerization in stressed cells by knocking down LIMK1 or expressing Cofilin, an inhibitor of F-actin elongation, blocks ROS production and JNK activation, hence AiP. Furthermore, Dronc and LIMK1 genetically interact. Co-expression of Dronc and LIMK1 drives F-actin accumulation, ROS production and JNK activation. Interestingly, these synergistic effects between Dronc and LIMK1 depend on Myo1D. Therefore, F-actin remodeling plays an important role mediating caspase-driven ROS production and JNK activation in the process of AiP.
Original language | English |
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Article number | e1010533 |
Number of pages | 24 |
Journal | PLoS Genetics |
Volume | 18 |
Issue number | 12 |
DOIs | |
Publication status | Published - 5 Dec 2022 |
Keywords
- Biology and life sciences
- Medicine and health sciences
- Physical sciences
- Research Article
- Research and analysis methods
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Dive into the research topics of 'Actin remodeling mediates ROS production and JNK activation to drive apoptosis-induced proliferation'. Together they form a unique fingerprint.Projects
- 2 Finished
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Actin Cytoskeleton Remodelling in Apoptosis-induced Proliferation and Tissue Growth Control
Fan, Y. (Principal Investigator)
Biotechnology & Biological Sciences Research Council
30/09/19 → 29/09/23
Project: Research Councils
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Determining cellular processes underlying apoptosis-induced cell proliferation through kinase analysis
Fan, Y. (Principal Investigator)
Biotechnology & Biological Sciences Research Council
1/08/15 → 31/01/19
Project: Research Councils