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Updated: Aug 22, 2025

Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy
Published on: August 19, 2021
Functional significance of ion channels during macropinosome resolution in immune cells
Masashi Maekawa1,2, Ren Natsume1,2, Makoto Arita1,2,3
1Division of Physiological Chemistry and Metabolism, Graduate School of Pharmaceutical Sciences, Keio University, Tokyo, Japan.
Abstract:
Macropinocytosis is a unique type of endocytosis accompanied by membrane ruffle formation. Closure of membrane ruffles leads to the uptake of large volumes of fluid phase and, subsequently, the formation of large vacuoles termed macropinosomes. Immune cells, such as dendritic cells, T cells, and macrophages, endocytose the surrounding amino acids and pathogens via macropinocytosis either constitutively or in a stimulus-dependent fashion. This process is critical for cell migration, mammalian target of rapamycin complex 1 (mTORC1) activation, and antigen presentation. Large vacuoles are fragmented into tubules and smaller vesicles during the progression and maturation of macropinosomes in immune cells. This process is called "macropinosome resolution" and requires osmotically driven shrinkage of macropinosomes, which is controlled by ion channels present in them. The crenation of membranes on shrunken macropinosomes is recognized by curvature-sensing proteins and results in intracellular membrane trafficking. In this mini review, we highlight the recent progress in research on macropinosome resolution in macrophages, with a focus on ion channels (TPC1/2 for Na+ and TMEM206 for Cl-) that is required for macropinosome resolution. We also discuss the potential contribution of membrane lipids to this process.
Insights
Macropinocytosis resolution in macrophages involves ion channels controlling macropinosome shrinkage. This process, crucial for immune cell function, relies on TPC1/2 and TMEM206 channels for effective macropinosome resolution.
Area of Science:
- Cell Biology
- Immunology
- Membrane Trafficking
Background:
- Macropinocytosis is a key endocytic pathway for immune cells, internalizing large fluid volumes and pathogens via macropinosomes.
- This process is vital for immune cell migration, mTORC1 activation, and antigen presentation.
- Macropinosome maturation involves fragmentation, termed macropinosome resolution, requiring osmotic shrinkage.
Purpose of the Study:
- To review recent advancements in understanding macropinosome resolution in macrophages.
- To highlight the role of specific ion channels in regulating macropinosome shrinkage and resolution.
- To discuss the potential involvement of membrane lipids in this cellular process.
Main Methods:
- Literature review focusing on macropinocytosis and macropinosome resolution mechanisms.
- Analysis of studies investigating ion channel function (TPC1/2, TMEM206) in macrophages.
- Discussion of research on membrane lipid contributions to membrane dynamics.
Main Results:
- Macropinosome resolution is driven by osmotically induced shrinkage.
- Ion channels, specifically TPC1/2 (Na+) and TMEM206 (Cl-), are critical regulators of this shrinkage.
- Curvature-sensing proteins interact with shrunken membranes, facilitating intracellular trafficking.
Conclusions:
- Ion channels are essential for controlling macropinosome resolution in macrophages.
- Understanding these channels and membrane dynamics offers insights into immune cell function.
- Further research into membrane lipids may reveal additional regulatory mechanisms.
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