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Updated: Sep 22, 2025

Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy
07:31

Measuring the pH, Redox Chemistries, and Degradative Capacity of Macropinosomes using Dual-Fluorophore Ratiometric Microscopy

Published on: August 19, 2021

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Proton-gated anion transport governs macropinosome shrinkage

Mariia Zeziulia1,2,3, Sandy Blin1,2, Franziska W Schmitt1,2,4

  • 1Leibniz-Forschungsinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany.

Nature Cell Biology
|May 19, 2022
PubMed

Insights

Researchers identified the ASOR/TMEM206 channel as crucial for regulating the size of macrophage macropinosomes by controlling ion and water transport. This discovery offers insights into vacuole maturation and cancer cell survival.

Area of Science:

  • Cell Biology
  • Membrane Transport
  • Physiology

Background:

  • Intracellular organelles, like macropinosomes, change size during maturation, necessitating ion and water transport across membranes.
  • Macropinocytosis is a vital endocytic process for immune and cancer cells, forming large, optically trackable vacuoles.
  • Macrophage macropinosome shrinkage relies on TPC-mediated sodium efflux and chloride exit via unidentified channels.

Purpose of the Study:

  • To identify the chloride channel responsible for macrophage macropinosome shrinkage.
  • To elucidate the regulatory mechanisms and biological roles of this chloride channel.

Main Methods:

  • Patch-clamp electrophysiology to characterize ion channel activity.
  • Genetic manipulation (TMEM206 disruption) to assess channel function in vivo.
  • Mathematical modeling to analyze feedback loops in vacuole maturation.
  • Cell survival assays.

Main Results:

  • The proton-activated chloride channel ASOR/TMEM206 was identified as the missing chloride channel in macrophage macropinosomes.
  • ASOR activation is dependent on sodium-mediated depolarization and luminal acidification by proton pumps and CLC exchangers.
  • Mathematical modeling confirmed feedback loops involving ASOR and CLC channels ensure vacuole resolution.
  • Disruption of TMEM206 enhanced albumin-dependent cancer cell survival.

Conclusions:

  • ASOR/TMEM206 plays a critical role in regulating macropinosome volume and maturation through voltage- and pH-dependent chloride transport.
  • The study provides a comprehensive model for ion transport in vacuole maturation.
  • ASOR/TMEM206 has significant biological implications, including a role in cancer cell survival.

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