Milk Fat Globule Membrane Proteomics: A 'Snapshot' of Mammary Epithelial Cell Biology

Lipids are released in milk as fat globules, which are droplets of apolar lipids surrounded by a complex membrane deriving from the mammary epithelial cell (MEC) and called the milk fat globule membrane (MFGM). The structure of the MFGM is highly complex and closely related to the mechanisms of milk fat globule secretion in the mammary epithelial cell. Indeed, MFGM is composed of two biological membranes, a phospholipid monolayer, deriving from the endoplasmic reticulum, and a phospholipid bilayer, which originates from the apical plasma membrane of the MEG, with variable amounts of cytoplasm trapped between. Biochemical techniques (i.e. sodium dodecyl sulphate-polyacrylamide gel electrophoresis followed by different staining procedures) have been employed historically to characterize major MFGM proteins, namely MUG-1, fatty acid synthase, xanthine oxidase, butyrophilin, lactadherin, and adipophilin. However, recent advances in the field of proteomics (mostly development of one-dimensional gel electrophoresis approach coupled with tandem mass spectrometry) have led to the identification of hundreds of proteins associated with the MFGM. Surprisingly, newly identified MFGM proteins were not only involved in lipid metabolic or exocytosis-related biological processes, but also in cell signalling, translation, or host defense-related mechanisms. Therefore, the milk fat globule should no longer be viewed as an inert structure only devoted to the delivery of lipids to the newborn, but rather as a dynamic and informative compartment which can contribute to the improvement of our comprehension of the mammary gland biology.