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Implementation of a Permeable Membrane Insert-based Infection System to Study the Effects of Secreted Bacterial Toxins on Mammalian Host Cells
Published on: August 19, 2016
Pore-forming bacterial toxins and antimicrobial peptides as modulators of ADAM function
Karina Reiss1, Sucharit Bhakdi
1Department of Dermatology, Christian-Albrecht University Kiel, 24098 Kiel, Germany. kreiss@dermatology.uni-kiel.de
Abstract:
Membrane-perturbating proteins and peptides are widespread agents in biology. Pore-forming bacterial toxins represent major virulence factors of pathogenic microorganisms. Membrane-damaging peptides constitute important antimicrobial effectors of innate immunity. Membrane perturbation can incur multiple responses in mammalian cells. The present discussion will focus on the interplay between membrane-damaging agents and the function of cell-bound metalloproteinases of the ADAM family. These transmembrane enzymes have emerged as the major proteinase family that mediate the proteolytic release of membrane-associated proteins, a process designated as "shedding". They liberate a large spectrum of functionally active molecules including inflammatory cytokines, growth factor receptors and cell adhesion molecules, thereby regulating such vital cellular functions as cell-cell adhesion, cell proliferation and cell migration. ADAM activation may constitute part of the cellular recovery machinery on the one hand, but likely also promotes inflammatory processes on the other. The mechanisms underlying ADAM activation and the functional consequences thereof are currently the subject of intensive research. Attention here is drawn to the possible involvement of purinergic receptors and ceramide generation in the context of ADAM activation following membrane perturbation by membrane-active agents.
Insights
Membrane-damaging agents activate ADAM metalloproteinases, influencing cell functions and inflammation. This research explores their role in cellular responses and recovery mechanisms.
Area of Science:
- Molecular biology
- Cell biology
- Biochemistry
Background:
- Membrane-perturbating proteins and peptides are crucial in biological processes, including bacterial virulence and innate immunity.
- These agents can trigger diverse responses in mammalian cells.
- ADAM (a disintegrin and metalloproteinase) family metalloproteinases are key enzymes mediating the shedding of membrane-bound proteins.
Purpose of the Study:
- To investigate the interaction between membrane-damaging agents and ADAM metalloproteinase function.
- To elucidate the role of ADAM activation in cellular responses to membrane perturbation.
- To explore potential mechanisms, such as purinergic receptors and ceramide generation, involved in ADAM activation.
Main Methods:
- Literature review and discussion of existing research on membrane-active agents and ADAM metalloproteinases.
- Analysis of cellular responses to membrane perturbation.
- Exploration of signaling pathways potentially regulating ADAM activation.
Main Results:
- ADAM metalloproteinases are central to the shedding process, releasing bioactive molecules that regulate cell adhesion, proliferation, and migration.
- ADAM activation can contribute to cellular recovery but also promote inflammation.
- Purinergic receptors and ceramide generation are implicated in ADAM activation following membrane damage.
Conclusions:
- Membrane perturbation by specific agents can modulate ADAM metalloproteinase activity.
- ADAMs play a dual role in cellular responses, potentially mediating both repair and inflammatory processes.
- Further research is needed to fully understand the mechanisms and consequences of ADAM activation in response to membrane damage.
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