Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance

Freeman SA, Uderhardt S, Saric A, Collins RF, Buckley CM, Mylvaganam S, Boroumand P, Plumb J, Germain RN, Ren D, Grinstein S (2020)

Publication Type: Journal article

Publication year: 2020

Journal

Science American Association for the Advancement of Science

Book Volume: 367

Pages Range: 301-305

Journal Issue: 6475

DOI: 10.1126/science.aaw9544

Abstract

Despite ongoing (macro)pinocytosis of extracellular fluid, the volume of the endocytic pathway remains unchanged. To investigate the underlying mechanism, we used high-resolution video imaging to analyze the fate of macropinosomes formed by macrophages in vitro and in situ. Na+, the primary cationic osmolyte internalized, exited endocytic vacuoles via two-pore channels, accompanied by parallel efflux of Cl− and osmotically coupled water. The resulting shrinkage caused crenation of the membrane, which fostered recruitment of curvature-sensing proteins. These proteins stabilized tubules and promoted their elongation, driving vacuolar remodeling, receptor recycling, and resolution of the organelles. Failure to resolve internalized fluid impairs the tissue surveillance activity of resident macrophages. Thus, osmotically driven increases in the surface-to-volume ratio of endomembranes promote traffic between compartments and help to ensure tissue homeostasis.

Authors with CRIS profile

Stefan Uderhardt Department of Medicine 3 – Rheumatology and Immunology

Involved external institutions

The Hospital for Sick Children (SickKids) CA Canada (CA) University of Pennsylvania US United States (USA) (US) National Institute of Allergy and Infectious Diseases US United States (USA) (US)

How to cite

APA:

Freeman, S.A., Uderhardt, S., Saric, A., Collins, R.F., Buckley, C.M., Mylvaganam, S.,... Grinstein, S. (2020). Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance. Science, 367(6475), 301-305. https://doi.org/10.1126/science.aaw9544

MLA:

Freeman, Spencer A., et al. "Lipid-gated monovalent ion fluxes regulate endocytic traffic and support immune surveillance." Science 367.6475 (2020): 301-305.

BibTeX: Download