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

Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works..

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.

Errataetall:

CommentIn: Science. 2020 Jan 17;367(6475):246-247. - PMID 31949066

Medienart:

E-Artikel

Erscheinungsjahr:

2020

Erschienen:

2020

Enthalten in:

Zur Gesamtaufnahme - volume:367

Enthalten in:

Science (New York, N.Y.) - 367(2020), 6475 vom: 17. Jan., Seite 301-305

Sprache:

Englisch

Beteiligte Personen:

Freeman, Spencer A [VerfasserIn]
Uderhardt, Stefan [VerfasserIn]
Saric, Amra [VerfasserIn]
Collins, Richard F [VerfasserIn]
Buckley, Catherine M [VerfasserIn]
Mylvaganam, Sivakami [VerfasserIn]
Boroumand, Parastoo [VerfasserIn]
Plumb, Jonathan [VerfasserIn]
Germain, Ronald N [VerfasserIn]
Ren, Dejian [VerfasserIn]
Grinstein, Sergio [VerfasserIn]

Links:

Volltext

Themen:

9NEZ333N27
Calcium Channels
Journal Article
Lipids
Mcoln1 protein, mouse
Research Support, N.I.H., Extramural
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't
Sodium
TPCN1 protein, mouse
TPCN2 protein, mouse
Transient Receptor Potential Channels

Anmerkungen:

Date Completed 19.05.2020

Date Revised 15.05.2021

published: Print-Electronic

CommentIn: Science. 2020 Jan 17;367(6475):246-247. - PMID 31949066

Citation Status MEDLINE

doi:

10.1126/science.aaw9544

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM304083550