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.

Frontiers in Physiology
|November 7, 2022
PubMed

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.

Related Concept Videos

Phosphoinositides and PIPs01:42

Phosphoinositides and PIPs

Phosphoinositides are a group of phospholipids containing a glycerol backbone with two fatty acid chains and a phosphate attached to a myoinositol sugar ring. The inositol head group extends into the cytoplasm, where it is modified by adding phosphate groups to form phosphatidylinositol phosphates or PIPs.
Different phosphoinositides are synthesized and recruited on the cytosolic face of the plasma membrane. The localization of specific phosphoinositides concentrated in separate membrane...
8.7K
Ion Channels01:19

Ion Channels

The movement of ions like sodium, potassium, and calcium into and out of the cell is essential to maintain the electrochemical gradient in living cells. The ion channels—a class of membrane transport proteins—help maintain this ionic gradient for the smooth functioning of physiological activities such as maintaining cell size and volume, conducting nerve impulses, and gas and nutrient exchange.
Ion channels are specialized integral membrane proteins on the plasma membrane that allow...
87.5K
Immune Surveillance by NK Cells and Phagocytes01:25

Immune Surveillance by NK Cells and Phagocytes

Immune surveillance is an integral part of the innate immune system, involving the continuous monitoring of peripheral tissues to detect and respond to pathogens, infected cells, or cancerous cells. This surveillance is conducted primarily by natural killer (NK) cells and phagocytes, which employ distinct but complementary mechanisms to identify and eliminate threats.
Natural Killer Cells: The Fast Responders
NK cells are large granular lymphocytes found in the blood and lymphatic system. These...
1.6K
Cells of the Innate Immune Response01:28

Cells of the Innate Immune Response

The innate immune response is an immediate and non-specific response against pathogens, acting swiftly to prevent the spread of infections. The primary cells involved in this response are phagocytes and natural killer (NK) cells.
Phagocytes
Phagocytes police the peripheral tissues by removing cellular debris and responding to the invasion of foreign substances or pathogens. Many phagocytes attack and remove microorganisms even before lymphocytes detect them. The human body has two general...
2.0K