Extracellular vesicle ‐mediated MFG‐E8 localization in the extracellular matrix is required for its integrin‐dependent function in mouse mammary epithelial cells

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 β‐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.

Mouse MFG‐E8 was transiently localized to the mammary basal lamina during involution. MFG‐E8 was connected extracellular matrix with...

Source: Genes to Cells - September 8, 2017 Category: Genetics & Stem Cells Authors: Takuya Ooishi, Daita Nadano, Tsukasa Matsuda, Kenzi Oshima Tags: Original Article Source Type: research