Sealing holes in cellular membranes

Abstract

The compartmentalization of eukaryotic cells, which is essential for their viability and functions, is ensured by single or double bilayer membranes that separate the cell from the exterior and form boundaries between the cell's organelles and the cytosol. Nascent nuclear envelopes and autophagosomes, which both are enveloped by double membranes, need to be sealed during the late stage of their biogenesis. On the other hand, the integrity of cellular membranes such as the plasma membrane, lysosomes and the nuclear envelope can be compromised by pathogens, chemicals, radiation, inflammatory responses and mechanical stress. There are cellular programmes that restore membrane integrity after injury. Here, we review cellular mechanisms that have evolved to maintain membrane integrity during organelle biogenesis and after injury, including membrane scission mediated by the endosomal sorting complex required for transport (ESCRT), vesicle patching and endocytosis.

Annexins and Membrane Repair Dysfunctions in Muscular Dystrophies

“…Studies of membrane repair-related processes are still the subject of intensive work, in particular to elucidate the mechanism(s) that take place depending on the cell type and the nature of the damage. Many reviews already exist on this topic [ 1 , 2 , 7 , 21 , 22 , 23 ]; here, we will focus on current understanding of membrane repair mechanisms in skeletal muscle cell.…”

“…Membrane ruptures induced by mechanical stress, such as contraction, stretching, or shearing, compromise cellular homeostasis and lead to cell death in the absence of fast resealing [ 1 , 2 ]. Frequency of cell membrane disruption is high in mammal tissues subjected to severe mechanical constraints, such as cardiac or skeletal muscle, epithelia, and endothelium [ 3 , 4 , 5 , 6 ].…”

“…Discrepancies in experimental data have been indeed observed, which may result from the existence of different repair mechanisms depending on the cell type and the damage nature. While a membrane lesion less than 0.2 μm can be repaired passively, tension exerted by actin cytoskeleton on plasma membrane induces larger lesions and requires the intervention of active repair mechanisms [ 1 , 2 ]. These mechanisms are mostly triggered by the influx of extracellular calcium (Ca 2+ ), which rushes into the cell through the membrane breach and invade the cytoplasm.…”

Oligomerization of Selective Autophagy Receptors for the Targeting and Degradation of Protein Aggregates

“…However, studies also showed that autophagosomes can correctly seal in the absence of Atg8-PE, which does not support the role of Atg8-PE in the closure of autophagosomal membranes [52][53][54]. Recently, several studies have shown that the endosomal sorting complexes required for transport (ESCRT) machinery plays a pivotal role in the closure of autophagosomal membranes [55][56][57][58]. Using the HaloTag-LC3 autophagosome completion assays, Takahashi et al found that ESCRT-III component CHMP2A traffics to the phagophore and promotes the separation of the inner and outer autophagosomal membranes, which eventually leads to the formation of sealed autophagosomes [59].…”

His domain protein tyrosine phosphatase and Rabaptin-5 couple endo-lysosomal sorting of EGFR with endosomal maturation

“…This series of protein complexes includes the ESCRTs-0, -I and -II, ubiquitin-binding complexes, which sequester ubiquitylated cargo and then pass it to ESCRT-III ( Frankel and Audhya, 2018 ; Henne et al, 2011 ; Piper et al, 2014 ). ESCRT-III is a generic membrane curvature-inducing polymer that combines with the downstream AAA ATPase VPS4 (VPS4A and VPS4B forms in mammals) to drive reverse topology membrane scission ( Gatta and Carlton, 2019 ; Henne et al, 2013 ; McCullough et al, 2018 ; Pfitzner et al, 2021 ; Remec Pavlin and Hurley, 2020 ; Zhen et al, 2021 ), and thus at the MVB completes ILV formation ( Raiborg and Stenmark, 2009 ; Vietri et al, 2020 ).…”