期刊
PROTEOMICS
卷 21, 期 13-14, 页码 -出版社
WILEY
DOI: 10.1002/pmic.202000091
关键词
calcium; cancer; cytoskeleton; extracellular vesicles; spectrin
This study examined the role of alpha II-spectrin in vesiculation of malignant and non-malignant plasma membrane, using high resolution confocal microscopy to evaluate its subcellular distribution. The results showed distinct differences in cortical spectrin localization between malignant and non-malignant cells at rest, suggesting that the redistribution of cortical alpha II-spectrin supports plasma membrane-derived EV biogenesis in malignant cells.
Spectrin is a ubiquitous cytoskeletal protein that provides structural stability and supports membrane integrity. In erythrocytes, spectrin proteolysis leads to the biogenesis of plasma membrane extracellular vesicles (EVs). However, its role in non-erythroid or cancer-derived plasma membrane EVs biogenesis is unknown. This study aims to examine the role of alpha II-spectrin in malignant and non-malignant plasma membrane vesiculation. We developed a custom, automated cell segmentation plugin for the image processor, Fiji, that provides an unbiased assessment of high resolution confocal microscopy images of the subcellular distribution of alpha II-spectrin. We show that, in low vesiculating non-malignant MBE-F breast cells, prominent cortical spectrin localises to the cell periphery at rest. In comparison, cortical spectrin is diminished in high vesiculating malignant MCF-7 breast cells at rest. A cortical distribution of spectrin correlates with increased biomechanical stiffness as measured by Atomic Force Microscopy. Furthermore, cortical spectrin can be induced in malignant MCF-7 cells by treatment with known vesiculation modulators including the calcium chelator, BAPTA-AM or the calpain inhibitor II (ALLM). These results demonstrate that the subcellular localisation of spectrin is distinctly different in malignant and non-malignant cells at rest and shows that the redistribution of cortical alpha II-spectrin to the cytoplasm supports plasma membrane-derived EV biogenesis in malignant cells.
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