Plasma membrane integrity in health and disease: significance and therapeutic potential

Abstract

Maintenance of plasma membrane integrity is essential for normal cell viability and function. Thus, robust membrane repair mechanisms have evolved to counteract the eminent threat of a torn plasma membrane. Different repair mechanisms and the bio-physical parameters required for efficient repair are now emerging from different research groups. However, less is known about when these mechanisms come into play. This review focuses on the existence of membrane disruptions and repair mechanisms in both physiological and pathological conditions, and across multiple cell types, albeit to different degrees. Fundamentally, irrespective of the source of membrane disruption, aberrant calcium influx is the common stimulus that activates the membrane repair response. Inadequate repair responses can tip the balance between physiology and pathology, highlighting the significance of plasma membrane integrity. For example, an over-activated repair response can promote cancer invasion, while the inability to efficiently repair membrane can drive neurodegeneration and muscular dystrophies. The interdisciplinary view explored here emphasises the widespread potential of targeting plasma membrane repair mechanisms for therapeutic purposes.

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.…”

“…The absence of membrane repair causes the death of damaged cells and may contribute to tissue degeneration and the development of degenerative diseases [ 1 ]. A defective membrane repair machinery is observed in MMD1 [ 8 , 9 ], LGMDR1 (formerly 2A) [ 10 ], LGMDR2 (2B) [ 8 ], LGMD1C [ 11 ], and LGMDR12 (2L) (see chapter 4 for the nomenclature of LGMD) [ 12 , 13 ].…”

Role of Exosomal MicroRNAs and Their Crosstalk with Oxidative Stress in the Pathogenesis of Osteoporosis

“…Exos are thought to be involved in many biological processes and play an important role in cell-to-cell communication [44][45][46]. Most cells release exos into the extracellular environment after plasma membrane fusion [47][48][49]. The discovery of exos dates back to 1983, when researchers cultured reticulocytes to track the movement of transferrin receptors from the plasma membrane to reticulocytes.…”