| First Author | Ooishi T | Year | 2017 |
| Journal | Genes Cells | Volume | 22 |
| Issue | 10 | Pages | 885-899 |
| PubMed ID | 28884934 | Mgi Jnum | J:318429 |
| Mgi Id | MGI:6859611 | Doi | 10.1111/gtc.12521 |
| Citation | Ooishi T, et al. (2017) Extracellular vesicle-mediated MFG-E8 localization in the extracellular matrix is required for its integrin-dependent function in mouse mammary epithelial cells. Genes Cells 22(10):885-899 |
| abstractText | Milk fat globule-EGF factor 8 (MFG-E8) is a divalent-binding secretory protein possessing an Arg-Gly-Asp (RGD) motif and a phosphatidylserine (PS)-binding motif. This protein has been shown to be involved in mammary gland development and morphogenesis. Integrin-binding activity is necessary for these MFG-E8-dependent cell processes. Although the target cells and molecules of MFG-E8 in the cellular microenvironment are important to understand its physiological function, its localization is largely unclear. Here, we found that mouse MFG-E8 localized to the basal lamina of the mammary gland during involution. In a model system of mammary COMMA-1D cells, exogenously and endogenously expressed MFG-E8 was deposited in the extracellular matrix (ECM) with membranous particles dependently on the PS-binding motifs in the discoidin domains that were essential for association ability to extracellular vesicles (EVs). These data showed the basal MFG-E8 localization mechanism in which EVs served as a scaffold. Such an immobilized MFG-E8 associating with cell substrata but not soluble one in the culture media promoted integrin-dependent suppression of beta-casein expression. These results suggest that MFG-E8 requires EVs to transduce cellular signals from the basolateral side of the adhesion cells by accumulating in ECM. |
