Plasma Membrane Lipid Domains as Platforms for Vesicle Biogenesis and Shedding?

Pollet, Hélène; Conrard, Louise; Cloos, Anne‐Sophie; Tyteca, Donatienne

doi:10.3390/biom8030094

Cited by 105 publications

(93 citation statements)

References 299 publications

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“…7: (1) actin and membrane from neighboring regions of the cell are relocated to the site of damage; (2) in a process dependent on F-actin nucleation and Myo1a, relocated membrane and actin are used to construct new filopodia-like protrusions to act as scaffolds for vesicle shedding; and (3) F-actin dynamics, Myo1a and the ESCRT machinery mediate membrane remodeling and scission to shed damaged membrane. Damage-induced plasma membrane shedding is thus more complex than current models depicting simple vesiculation from flat plasma membrane domains 13, 45 . Interestingly, tufts of microvilli-like plasma membrane protrusions were previously reported in bovine retinal microvascular endothelial (BRME) cells in response to wounding 5 , and filopodia-like protrusions were observed in epithelial cells of Drosophila embryos upon wounding and were demonstrated to be important for healing 46 .…”

Section: Discussionmentioning

confidence: 92%

Plasma membrane damage removal by F-actin-mediated shedding from repurposed filopodia

Mageswaran

Yang

Chakrabarty

et al. 2019

Preprint

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26Repairing plasma membrane damage is vital to eukaryotic cell survival. Membrane shedding is 27 thought to be key to this repair process, but a detailed view of how the process occurs is still 28 missing. Here we used electron cryotomography to image the ultrastructural details of plasma 29 membrane wound healing. We found that filopodia-like protrusions are built at damage sites, 30 accompanied by retraction of neighboring filopodia, and that these repurposed protrusions act 31 as scaffolds for membrane shedding. This suggests a new role for filopodia as reservoirs of 32 membrane and actin for plasma membrane damage repair. Damage-induced shedding was 33 dependent on F-actin dynamics and Myo1a, as well as Vps4B, an important component of the 34ESCRT machinery. Thus we find that damage shedding is more complex than current models of 35 simple vesiculation from flat membrane domains. Rather, we observe structural similarities 36 between damage-mediated shedding and constitutive shedding from enterocytes that argue for 37 conservation of a general membrane shedding mechanism. 38 Main 39Maintaining the integrity of the plasma membrane is critical for the survival of eukaryotic cells, 40 and cells exhibit a rapid response to plasma membrane injury. Injury may include mechanical 41 damage, chemical insults or the introduction of foreign pore-forming proteins such as the 42 bacterial toxin streptolysin O (SLO) or the perforin secreted by cytotoxic T lymphocytes and 43 natural killer cells 1-3 . Laser ablation of the plasma membrane elicits similar responses 2 . 44Following damage, a rapid influx of Ca 2+ and ensuing exocytosis of lysosomes occurs 4-6 and the 45 membrane is resealed within a few seconds to a few minutes. Several models, not mutually 46 exclusive, have been proposed for how resealing occurs: (1) in what is known as the "patch 47 model", a damaged region is replaced by fusion of an intracellular vesicle with the plasma 48 membrane, sloughing off the damaged membrane in the process 7 ; (2) in the endocytic model, 49 damaged regions are internalized by endocytosis 3, 8 ; and (3) in the shedding model, damaged 50 regions bud from the plasma membrane and are shed as extracellular vesicles 2 . While the patch 51 model has not yet been validated experimentally, evidence exists for both endocytosis and52shedding. For example, SLO-induced pores have been shown to be eliminated by both 53 endocytosis 9 and shedding 1, 10, 11 . Several pieces of recent evidence suggest that shedding may 54 be the dominant mechanism for plasma membrane resealing. First, repair occurs even at low 55 temperature, a condition that stalls other mechanisms, including endocytosis 12 . Second, after 56 SLO treatment, SLO-containing vesicles are released in an annexin-dependent process 10, 11 . 57Third, extracellular vesicle-like structures are observed by scanning electron microscopy (SEM) 58 at sites of laser damage 2 . And finally, Endosomal Sorting Complexes Required for Transport 59 (ESCRT), known to be involved in membrane remodeling...

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Section: Discussionmentioning

confidence: 92%

Plasma membrane damage removal by F-actin-mediated shedding from repurposed filopodia

Mageswaran

Yang

Chakrabarty

et al. 2019

Preprint

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“…In many cases, in fact, the latter cells operate by the described basic and functional mechanisms, analogous to the cells of other types. The results [2][3][4][5][6]. A subsequent section also concerns specific diseases, including cancer, in which immune cells often play key roles.…”

Section: Extracellular Vesicles: Functions In General Cell Biology Anmentioning

confidence: 98%

“…A final section deals with the relevance of EVs in the diagnosis and therapy of those diseases [3,[5][6][7]12]. The results [2][3][4][5][6]. In (a) an exosome and an ectosome are directly bound to cell surface signalling receptors.…”

Section: Extracellular Vesicles: Functions In General Cell Biology Anmentioning

confidence: 99%

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Extracellular vesicles, news about their role in immune cells: physiology, pathology and diseases

Meldolesi

2019

Clinical and Experimental Immunology

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Two types of extracellular vesicles (EVs), exosomes and ectosomes, are generated and released by all cells, including immune cells. The two EVs appear different in many properties: size, mechanism and site of assembly, composition of their membranes and luminal cargoes, sites and processes of release. In functional terms, however, these differences are minor. Moreover, their binding to and effects on target cells appear similar, thus the two types are considered distinct only in a few cases, otherwise they are presented together as EVs. The EV physiology of the various immune cells differs as expected from their differential properties. Some properties, however, are common: EV release, taking place already at rest, is greatly increased upon cell stimulation; extracellular navigation occurs adjacent and at distance from the releasing cells; binding to and uptake by target cells are specific. EVs received from other immune or distinct cells govern many functions in target cells. Immune diseases in which EVs play multiple, often opposite (aggression and protection) effects, are numerous; inflammatory diseases; pathologies of various tissues; and brain diseases, such as multiple sclerosis. EVs also have effects on interactive immune and cancer cells. These effects are often distinct, promoting cytotoxicity or proliferation, the latter together with metastasis and angiogenesis. Diagnoses depend on the identification of EV biomarkers; therapies on various mechanisms such as (1) removal of aggression-inducing EVs; (2) EV manipulations specific for single targets, with insertion of surface peptides or luminal miRNAs; and (3) removal or re-expression of molecules from target cells.

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“…Lipid transporters such as ABCA3 1 are also involved in Exo production (75). Thus, Exo carry bioactive lipids, related enzymes, fatty acid transporters, and lipidrelated enzyme carriers and use lipids to fuse with target cells (76)(77)(78).…”

Section: Exosome Compositionmentioning

confidence: 99%