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

Area of Science:

• Cell Biology
• Membrane Biology
• Biochemistry

Background:

• Endosomal Sorting Complex Required for Transport (ESCRT) proteins are known to transiently interact with the plasma membrane for cellular processes like membrane repair and extracellular vesicle (EV) formation.
• The precise mechanisms and structures involved in these plasma membrane events are not fully understood.

Purpose of the Study:

• To investigate the novel, stable, micrometer-sized ESCRT structures observed at the plasma membrane.
• To elucidate the function and formation mechanism of these persistent ESCRT structures in various cell types.

Main Methods:

• Microscopy to visualize ESCRT structures in macrophages, dendritic cells, and fibroblasts.
• Analysis of ESCRT structure association with integrins and EV cargoes.
• Biochemical assays to assess phospholipid composition and actin cytoskeleton integrity.
• Experiments involving disruption of actin polymerization and exposure to silica crystals.

Main Results:

• Discovered stable, micrometer-sized, worm-shaped ESCRT structures persisting for hours at the plasma membrane.
• These structures ensheathed integrin clusters and EV cargoes, remaining attached to shed membrane patches.
• Observed altered phospholipid composition and local actin degradation at ESCRT structure sites.
• Increased ESCRT structure formation and cell adhesion upon disruption of actin polymerization.
• ESCRT structures were also found at sites of contact with membrane-disrupting silica crystals.

Conclusions:

• ESCRT proteins form stable structures at the plasma membrane, associated with membrane damage and EV formation.
• These structures appear to mediate the shedding of damaged membrane patches, potentially in response to adhesion-induced tears or foreign materials.
• The findings suggest a novel role for ESCRT proteins in large-scale membrane repair and extracellular shedding mechanisms.