Biology:Exopher
Exophers are a type of membrane-bound extracellular vesicle (EV) that are released by budding out of cells into the extracellular space. Exophers can be released by neurons[1] and muscle[2] in the nematode Caenorhabditis elegans and also from murine cardiomyocytes.[3] Exophers were first discovered in 2017 in the lab of Monica Driscoll at Rutgers University.[4]
Exophers are notable for their large size, averaging approximately four microns in diameter, and they are able to expel whole organelles, such as mitochondria and lysosomes as cargo.[1] An exopher can initially remain attached to the cell that produced it by a membranous filament that resembles a tunneling nanotube. Exophers share similarities with large oncosomes, but they differ in that they are produced by physiologically normal cells instead of aberrant cells associated with tumors.[5]
Exopher production is thought to be a mechanism cells use to preserve homeostasis. Exophers are produced in response to numerous stressors including intracellular protein aggregation, reactive oxygen species (ROS),[1] heat, osmotic hyertonicity, starvation,[6] and even space flight.[7] Extracellular signaling receptor MERTK, expressed by cardiac-resident macrophages, is necessary for exopher clearance by phagocytosis in mouse-derived cardiac tissue.[3]
Exophers may be relevant to disease. In mouse heart, eliminating macrophages or blocking their ability to engulf exophers lead to inflammation and ventricular dysregulation.[3] Exophers may also promote pathological protein spreading in neurodegenerative diseases due to their ability to carry aggregated proteins outside of neurons, including human huntingtin protein.[1]
References
- ↑ 1.0 1.1 1.2 1.3 Melentijevic, I; Toth, ML; Arnold, ML; Guasp, RJ; Harinath, G; Nguyen, KC; Taub, D; Parker, JA et al. (2017). "C. elegans neurons jettison protein aggregates and mitochondria under neurotoxic stress". Nature 542(7641) (7641): 367–371. doi:10.1038/nature21362. PMID 28178240. Bibcode: 2017Natur.542..367M.
- ↑ Turek, M; Banasiak, K; Piechota, M; Shanmugam, N; Macias, M; Śliwińska, MA; Niklewicz, M; Kowalski, K et al. (2021). "Muscle-derived exophers promote reproductive fitness". EMBO Rep. 22 (8). doi:10.15252/embr.202052071. PMID 34288362.
- ↑ 3.0 3.1 3.2 "A Network of Macrophages Supports Mitochondrial Homeostasis in the Heart". Cell 183 (1): 94–109. 2020. doi:10.1016/j.cell.2020.08.031. PMID 32937105.
- ↑ Neff, Ellen P. (2017-04-19). "C. elegans takes out the trash" (in en). Lab Animal 46 (5): 189. doi:10.1038/laban.1264. ISSN 1548-4475. https://www.nature.com/articles/laban.1264.
- ↑ "Oncosomes - large and small: what are they, where they came from?". Journal of Extracellular Vesicles 5. 2016. doi:10.3402/jev.v5.33109. PMID 27680302.
- ↑ Cooper, JF; Guasp, RJ; Arnold, ML; Grant, BD; Driscoll, M (2021). "Stress increases in exopher-mediated neuronal extrusion require lipid biosynthesis, FGF, and EGF RAS/MAPK signaling". Proc Natl Acad Sci USA 118 (36). doi:10.1073/pnas.2101410118. PMID 34475208. Bibcode: 2021PNAS..11801410C.
- ↑ "Spaceflight affects neuronal morphology and alters transcellular degradation of neuronal debris in adult Caenorhabditis elegans". iScience 24 (2). 2021. doi:10.1016/j.isci.2021.102105. PMID 33659873. Bibcode: 2021iSci...24j2105L.
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