In COS-7 cells overexpressing ESCRT-III proteins, micrometer-sized spirals are formed at the plasma membrane ( Cashikar et al., 2014). These wound-closing ESCRT accumulations appear as scattered puncta of up to 2 μm in size at membrane regions damaged by a laser or pore forming agent ( Jimenez et al., 2014 Scheffer et al., 2014).
For plasma membrane repair, the membrane remodeling polymers of the ESCRT-III subfamily are proposed to trap the damaged part of the membrane on buds that are pinched off. For example, ESCRT proteins are also involved in the repair of the nuclear membrane ( Denais et al., 2016 Raab et al., 2016) and the plasma membrane ( Jimenez et al., 2014 Scheffer et al., 2014 Ritter et al., 2022).
Whilst ESCRTs have long been known to regulate the formation of intraluminal vesicles in multivesicular bodies (MVBs Katzmann et al., 2001), additional roles for ESCRT proteins keep being identified. We propose that the ESCRT proteins are recruited to adhesion-induced membrane tears to induce extracellular shedding of the damaged membrane.Įndosomal Sorting Complex Required for Transport (ESCRT) proteins are critical membrane remodeling proteins found in all domains of life ( Lindås et al., 2008 Samson et al., 2008 Liu et al., 2021). The ESCRT structures were also present at plasma membrane contact sites with membrane-disrupting silica crystals. Disruption of actin polymerization increased the formation of the ESCRT structures and cell adhesion. 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. The ESCRT structures are tightly connected to the cellular support and are left behind by the cells together with surrounding patches of membrane. These structures surround clusters of integrins and known cargoes 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. Endosomal Sorting Complex Required for Transport (ESCRT) proteins can be transiently recruited to the plasma membrane for membrane repair and formation of extracellular vesicles.
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