Giant worm-shaped ESCRT scaffolds surround actin-independent integrin clusters

Femmy C. Stempels, Muwei Jiang, Harry M. Warner, Magda Lena Moser, Maaike H. Janssens, Sjors Maassen, Iris H. Nelen, Rinse de Boer, William F. Jiemy, David Knight, Julian Selley, Ronan O’Cualain, Maksim V. Baranov, Thomas C.Q. Burgers, Roberto Sansevrino, Dragomir Milovanovic, Peter Heeringa, Matthew C. Jones, Rifka Vlijm, Martinter BeestGeert van den Bogaart

Research output: Contribution to journalArticlepeer-review

Abstract

Endosomal Sorting Complex Required for Transport (ESCRT) proteins can be transiently recruited to the plasma membrane for membrane repair and formation of extracellular vesicles. Here, we discovered micrometer-sized worm-shaped ESCRT structures that stably persist for multiple hours at the plasma membrane of macrophages, dendritic cells, and fibroblasts. These structures surround clusters of integrins and known cargoes of extracellular vesicles. The ESCRT structures are tightly connected to the cellular support and are left behind by the cells together with surrounding patches of membrane. The phospholipid composition is altered at the position of the ESCRT structures, and the actin cytoskeleton is locally degraded, which are hallmarks of membrane damage and extracellular vesicle formation. Disruption of actin polymerization increased the formation of the ESCRT structures and cell adhesion. The ESCRT structures were also present at plasma membrane contact sites with membrane-disrupting silica crystals. We propose that the ESCRT proteins are recruited to adhesion-induced membrane tears to induce extracellular shedding of the damaged membrane.

Original languageEnglish
Article numbere202205130
JournalJournal of Cell Biology
Volume222
Issue number7
Early online date18 May 2023
DOIs
Publication statusPublished - 3 Jul 2023

Keywords

  • Actins/metabolism
  • Cell Membrane
  • Dendritic Cells
  • Endosomal Sorting Complexes Required for Transport/genetics
  • Fibroblasts
  • Humans
  • Integrins/genetics
  • Macrophages
  • Phospholipids/chemistry
  • Protein Conformation
  • Protein Transport

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