King et al., Science 2020

Water loss regulates cell and vesicle volume

Jason S. King and Elizabeth Smythe wrote a preview to our recent paper in Science.

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SUMMARY When cells take up extracellular fluid by endocytosis, they internalize a considerable proportion of the cell volume quickly and yet maintain their volume and ionic composition. This is particularly striking in the case of macropinocytosis, which is the bulk uptake of extracellular fluid. Through this pathway, macrophages can be stimulated to internalize ∼25% of their cellular volume per hour into large vacuoles known as macropinosomes. An intriguing question is how cells and organelles are able to maintain their size while internalizing such large volumes. On page 301 of this issue, Freeman et al. reveal a molecular mechanism underpinning homeostatic regulation of cell size. They demonstrate that newly formed macropinosomes rapidly lose volume by osmosis driven by two-pore channel (TPC)–mediated outflow of sodium ions. This reduces hydrostatic pressure within the macropinosome, facilitating the extension of tubules from the macropinosome surface and recycling of membrane lipids and proteins back to the cell surface.