Plasma Membrane Repair: A Central Process for Maintaining Cellular Homeostasis - PubMed (original) (raw)

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Plasma Membrane Repair: A Central Process for Maintaining Cellular Homeostasis

Alisa D Blazek et al. Physiology (Bethesda). 2015 Nov.

Abstract

Plasma membrane repair is a conserved cellular response mediating active resealing of membrane disruptions to maintain homeostasis and prevent cell death and progression of multiple diseases. Cell membrane repair repurposes mechanisms from various cellular functions, including vesicle trafficking, exocytosis, and endocytosis, to mend the broken membrane. Recent studies increased our understanding of membrane repair by establishing the molecular machinery contributing to membrane resealing. Here, we review some of the key proteins linked to cell membrane repair.

©2015 Int. Union Physiol. Sci./Am. Physiol. Soc.

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Conflict of interest statement

Noah Weisleder is Founder and Chief Scientific Officer of TRIM-edicine, a biotechnology company developing products targeting membrane repair, including rhMG53.

Figures

FIGURE 1.

FIGURE 1.

Models of the plasma membrane repair process A: thermodynamic resealing occurs spontaneously due to tension produced by the disordered arrangement of the membrane phospholipids at the open edge of the break. This process is the most likely route of resealing for membrane breaks of ≤1 μm in diameter. B: exocytosis can contribute by trafficking intracellular vesicles to the wounded area where they can fuse with each other and the injured membrane to form a repair patch. C: wound constriction is mediated by caveolae. During this process, caveolae cluster and fuse around larger wounds, leading to wound constriction and intracellular fusion of caveolar endosomes. D: budding/blebbing of the membrane portion containing the wound site with release of the newly formed vesicles into the extracellular space also involves exocytosis. E: exocytosis of an intracellular patch and fusion to the wound site could result in the extracellular release or “shedding” of the wound site. F: endocytosis of wounds occurs via invagination of caveolar vesicles and subsequent intracellular fusion of caveolae.

FIGURE 2.

FIGURE 2.

Major membrane repair proteins and their hypothesized roles in the repair process Dysferlin's interaction with AHNAK is regulated by calpain, and cleavage of dysferlin can result in additional subunits that function in repair. Calpain may also regulate cytoskeletal structure and sarcomere remodeling. AHNAK may aid in cytoskeletal remodeling. MG53/TRIM72 and dysferlin form a vesicle lattice to close the wound. A: affixin, which also binds dysferlin, localizes to focal adhesions and may organize actin. B: ESCRT and acid sphingomyelinase (ASM) facilitate exocytosis and endocytosis. ESCRT has been found to be involved in both endocytosis and budding. ESCRT III can be recruited to the membrane, followed by blebbing of the membrane and shedding of the wound. ASM is secreted and cleaves sphingomyelin to generate ceramide, leading to membrane invagination of the injury site. C: the annexin and S100A10 complex binds dysferlin and may recruit AHNAK to the membrane due to annexin's ability to bind lipid rafts. Annexin/S100A10 may also bridge adjacent phospholipids to form endosomes. Annexin accumulates at the neck of membrane blebs to mediate microvesicle release. Annexin A6 may also “cap” the membrane repair patch. D: synaptotagmin and SNARE proteins interact at the plasma membrane via a conformational change in synaptotagmin present on synaptic vesicles to fuse the vesicles with the membrane.

FIGURE 3.

FIGURE 3.

Proposed roles of MG53/TRIM72 in mediating membrane repair MG53/TRIM72 interacts with phosphatidylserine in the plasma membrane in a complex containing dysferlin and Cav-3. MG53/TRIM72 and dysferlin close the membrane wound with vesicles. Vesicle transport is facilitated by myosin motor proteins. Cav-3 may regulate MG53/TRIM72-mediated membrane fusion and is enriched in caveolae or plasma membrane invaginations. PTRF may aid in the formation and stabilization of these caveolae by interaction with Cav-3 and MG53/TRIM72 through cholesterol. PTRF also binds and may help localize dysferlin.

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References

    1. Ampong BN, Imamura M, Matsumiya T, Yoshida M, Takeda S. Intracellular localization of dysferlin and its association with the dihydropyridine receptor. Acta Myol 24: 134–144, 2005. - PubMed
    1. Anderson LV, Davison K, Moss JA, Young C, Cullen MJ, Walsh J, Johnson MA, Bashir R, Britton S, Keers S, Argov Z, Mahjneh I, Fougerousse F, Beckmann JS, Bushby KM. Dysferlin is a plasma membrane protein and is expressed early in human development. Hum Mol Genet 8: 855–861, 1999. - PubMed
    1. Babiychuk EB, Draeger A. Annexins in cell membrane dynamics. Ca2+-regulated association of lipid microdomains. J Cell Biol 150: 1113–1124, 2000. - PMC - PubMed
    1. Babiychuk EB, Monastyrskaya K, Potez S, Draeger A. Intracellular Ca2+ operates a switch between repair and lysis of streptolysin O-perforated cells. Cell Death Differ 16: 1126–1134, 2009. - PubMed
    1. Bansal D, Miyake K, Vogel SS, Groh S, Chen CC, Williamson R, McNeil PL, Campbell KP. Defective membrane repair in dysferlin-deficient muscular dystrophy. Nature 423: 168–172, 2003. - PubMed

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