Early Endosomes Act as Local Exocytosis Hubs to Repair Endothelial Membrane Damage

The plasma membrane of a cell is subject to stresses causing ruptures that must be repaired immediately to preserve membrane integrity and ensure cell survival. Yet, the spatio-temporal membrane dynamics at the wound site and the source of the membrane required for wound repair are poorly understood. Here, it is shown that early endosomes, previously only known to function in the uptake of extracellular material and its endocytic transport, are involved in plasma membrane repair in human endothelial cells. Using live-cell imaging and correlative light and electron microscopy, it is demonstrated that membrane injury triggers a previously unknown exocytosis of early endosomes that is induced by Ca2+ entering through the wound. This exocytosis is restricted to the vicinity of the wound site and mediated by the endosomal soluble N-ethylmaleimide sensitive factor attachment protein receptor (SNARE) VAMP2, which is crucial for efficient membrane repair. Thus, the newly identified Ca2+-evoked and localized exocytosis of early endosomes supplies the membrane material required for rapid resealing of a damaged plasma membrane, thereby providing the first line of defense against damage in mechanically challenged endothelial cells.

Automated summary

The plasma membrane of a cell undergoes stresses that cause ruptures, which need immediate repair to maintain membrane integrity. The mechanism of repairing the membrane and the source of membrane material for this repair are poorly understood. This study reveals that early endosomes, previously known for their role in endocytic transport, are involved in the repair of plasma membrane in human endothelial cells. The researchers demonstrate that membrane injury triggers a previously unknown exocytosis of early endosomes, which is induced by Ca2+ entering through the wound. This Ca2+-evoked and localized exocytosis of early endosomes, mediated by the SNARE protein VAMP2, provides the membrane material required for the rapid resealing of the damaged plasma membrane.