Migrasomes: the knowns, the known unknowns and the unknown unknowns: a personal perspective
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grasomes: the knowns, the known unknowns and the unknown unknowns: a personal perspective *
Li Yu
The State Key Laboratory of Membrane Biology, Tsinghua University-Peking University Joint Centre for Life Sciences, Beijing Frontier Research Center for Biological Structure, School of life Sciences, Beijing, China Received July 9, 2020; accepted September 29, 2020; published online November 12, 2020
Citation:
Yu, L. (2020). Migrasomes: the knowns, the known unknowns and the unknown unknowns: a personal perspective. Sci China Life Sci 63, https://doi. org/10.1007/s11427-020-1827-8
I still remember the day. It was 2012. I was checking the transmission electron microscopy images from the previous day. Something unusual caught my eyes. A structure closely resembling an opened pomegranate stood outside a cell. In retrospect, I realized I had seen these structure before, but that particular image was unusual because there were several of these large structures outside the cell. Some of them were empty, some of them had a few vesicles inside, and some of them were packed with vesicles. Just that day, provoked by that particularly striking image, I started to wonder what these structures were. Fragments of dead cells? Too neat. Exosomes? Too big. Shedding vesicles? Maybe. If so, what are the vesicles inside? Starting from this TEM image, we began our journey to understanding the pomegranate-like structure (PLS), as it was soon called in my lab at that time. To identify a PLS marker protein, we isolated PLSs by subcellular fractionation. We performed mass spectrometry to give us a list of candidate proteins enriched on isolated PLSs. By using GFP-tagged candidate proteins, we very soon identified proteins enriched on PLSs. Among them, Tetraspanin4 (Tspan4) stood as a good marker, as it is highly enriched in PLSs. What really surprised us is that Tspan4 also labels an extensive network of membrane tethers connected to the trailing edge of the cell, with PLSs located at the branch points or the ends of the tethers. The overall appearance is of an integrated circuit (Figure 1A). A quick
literature search told us that these tethers are retraction fibers, which were first identified in 1963 (Taylor and Robbins, 1963). However, there was no mention of the PLS at all. Using GFP-tagged Tspan4, we carried out time-lapse imaging to monitor the biogenesis process of PLSs. It was soon clear to us that PLS formation is linked to cell migration. When cells migrate, retraction fibers are pulled out of the rear, and PLSs start to grow on the tips or the intersections of retraction fibers. Eventually, when the cell migrates away, the retraction fibers break and PLSs are detached from the cells. Because the formation of PLSs is dependent on migration, we re-named PLSs as migrasomes (Ma et al., 2015). The immediate question for us was what are the functions of migrasomes? We couldn’t really address this question at that stage of the study, since we didn’t even know whether migrasomes existed in vivo. We circumvented this problem by instead a
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