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Two-pore channel regulators - Who is in control?
Rebecca Deutsch1, Veronika Kudrina1, Marc Freichel2,3
1Walther Straub Institute of Pharmacology and Toxicology, Faculty of Medicine, Ludwig-Maximilians-University, Munich, Germany.
Frontiers in Physiology
|January 27, 2025
Summary
Two-pore channels (TPCs) regulate immune cell functions like exocytosis and phagocytosis. Adenine nucleotides and phosphoinositides modulate TPCs, impacting inflammation and anaphylaxis.
Area of Science:
- Immunology
- Cell Biology
- Molecular Physiology
Background:
- Two-pore channels (TPCs) are ion channels regulated by adenine nucleotides and phosphoinositides.
- TPCs are expressed in various immune cells, including macrophages, mast cells, and T cells.
- Their roles in immune responses are increasingly recognized.
Purpose of the Study:
- To review the diverse functions of TPCs in immune cell activity.
- To discuss the involvement of adenine nucleotides (NAADP, ATP) in TPC-mediated processes.
- To highlight recent discoveries regarding TPC regulatory proteins.
Main Methods:
- Literature review of studies on TPCs in immune cells.
- Analysis of experimental data on TPC function in macrophages, mast cells, and T cells.
- Examination of molecular mechanisms involving TPC regulators.
Main Results:
- TPCs regulate cytotoxic T cell exocytosis and mast cell degranulation.
- TPC modulation impacts regulatory T cell numbers and anti-inflammatory effects.
- TPCs are implicated in macrophage phagocytosis and phagosome resolution.
- Adenine nucleotides (NAADP, ATP) and phosphoinositides (PI(3,5)P2) are key regulators.
Conclusions:
- TPCs play critical roles in both innate and adaptive immunity.
- Understanding TPC regulation by nucleotides and auxiliary proteins is crucial for immune function.
- Further research into TPC regulatory networks may reveal therapeutic targets.
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