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Diverse plasma membrane protrusions act as platforms for extracellular vesicle shedding - PubMed

Review

Diverse plasma membrane protrusions act as platforms for extracellular vesicle shedding

Kirsi Rilla. J Extracell Vesicles. 2021 Sep.

Abstract

Plasma membrane curvature is an important factor in the regulation of cellular phenotype and is critical for various cellular activities including the shedding of extracellular vesicles (EV). One of the most striking morphological features of cells is different plasma membrane-covered extensions supported by actin core such as filopodia and microvilli. Despite the various functions of these extensions are partially unexplained, they are known to facilitate many crucial cellular functions such as migration, adhesion, absorption, and secretion. Due to the rapid increase in the research activity of EVs, there is raising evidence that one of the general features of cellular plasma membrane protrusions is to act as specialized platforms for the budding of EVs. This review will focus on early observations and recent findings supporting this hypothesis, discuss the putative budding and shedding mechanisms of protrusion-derived EVs and their biological significance.

Keywords: actin; extracellular vesicle; filopodium; microvillus; shedding.

© 2021 The Authors. Journal of Extracellular Vesicles published by Wiley Periodicals, LLC on behalf of the International Society for Extracellular Vesicles.

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Conflict of interest statement

There is no conflict of interest regarding the publication of this article.

Figures

FIGURE 1
FIGURE 1

Origins of different classes of extracellular vesicles. Exosomes are formed by exocytosis of multivesicular bodies of endosomal origin and microvesicles or ectosomes are formed by the outward blebbing, shedding, pearling or scission of the plasma membrane or its various protrusions

FIGURE 2
FIGURE 2

Examples of different cell types that generate EVs from their diverse plasma membrane protrusions and extensions

FIGURE 3
FIGURE 3

A schematic illustration of different plasma membrane protrusions that potentially act as platforms for the shedding of EVs. Protrusion‐derived EVs are generated by shedding from tips of filopodia or microvilli, from migrating cells as migrasomes, by pearling/vesiculation of retraction fibres, or via nanotubes

FIGURE 4
FIGURE 4

Scanning electron microscopy of cultured cells that release EVs from different protrusions: Plasma membrane budding (a), shedding or pearling of filopodia and retraction fibres (b‐d), migrasomes of migrating cells (e, f), and tunneling nanotubes (g‐i). MKN74 gastric cancer cells are shown in a, e, and f, human mesenchymal stem cells in b‐d, and primary mesothelial cells in g‐i. Arrows point filopodia and other protrusions and arrowheads indicate EVs of variable size in all panels. A big vesicle on the tip of a long tunneling nanotube from panel h is shown in the panel i at higher magnification (arrowhead in h and i)

FIGURE 5
FIGURE 5

Correlative light and electron microscopy (CLEM) of cultured bone marrow‐derived human mesenchymal stem cells. The cells have numerous CD44‐positive filopodia (a, red) that have a hyaluronan coating (b, green). SEM image is shown in c and overlay is shown in d. Panels e‐h show higher magnification of a pearling protrusion, positive for CD44 (red) and hyaluronan (green). Arrows point EV shedding from retraction fibres (arrows in panel c) and pearling or vesiculation of protrusions (arrows in panel g)

FIGURE 6
FIGURE 6

Confocal time‐lapse live‐cell imaging demonstrates the shedding of EVs from the tips of plasma membrane protrusions (arrows). Images in all time points show 3D maximum intensity projections created from stacks of confocal optical sections. One edge of a live MCF7 breast cancer cell is shown

FIGURE 7
FIGURE 7

A sphere of live GFP‐HAS3 expressing MCF‐7 breast cancer cells grown in 3D collagen gel. HAS3 expression induces the formation of extremely long filopodia and secretion of EVs from their tips. EVs are visualized in high numbers because they are trapped inside the gel. The image shows a maximum intensity projection created from a stack of confocal optical sections

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References

    1. Ahmed, S., Goh, W. I., & Bu, W. (2010). I‐BAR domains, IRSp53 and filopodium formation. Seminars in Cell & Developmental Biology, 21, 350–356. - PubMed
    1. Albrecht‐Buehler, G. (1980). Autonomous movements of cytoplasmic fragments. Proceedings of the National Academy of Sciences of the United States of America, 77, 6639–6643. - PMC - PubMed
    1. Ando, H., Niki, Y., Ito, M., Akiyama, K., Matsui, M. S., Yarosh, D. B., & Ichihashi, M. (2012). Melanosomes are transferred from melanocytes to keratinocytes through the processes of packaging, release, uptake, and dispersion. Journal of Investigative Dermatology, 132, 1222–1229. - PubMed
    1. Arasu, U. T., Kärnä, R., Härkönen, K., Oikari, S., Koistinen, A., Kröger, H., Qu, C., Lammi, M. J., & Rilla, K. (2017). Human mesenchymal stem cells secrete hyaluronan‐coated extracellular vesicles. Matrix Biology, 64, 54–68. - PubMed
    1. Arasu, U. T., Deen, A. J., Pasonen‐Seppänen, S., Heikkinen, S., Lalowski, M., Kärnä, R., Härkönen, K., Mäkinen, P., Lázaro‐Ibáñez, E., Siljander, P. R. M., Oikari, S., Levonen, A.‐L., & Rilla, K. (2020). HAS3‐induced extracellular vesicles from melanoma cells stimulate IHH mediated c‐Myc upregulation via the hedgehog signaling pathway in target cells. Cellular and Molecular Life Sciences, 77(20), 4093–4115. - PMC - PubMed

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