The Milk fat globule membrane

Patton, Stuart; Keenan, T.W.

doi:10.1016/0304-4157(75)90011-8

Cited by 364 publications

(152 citation statements)

References 158 publications

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“…MFGs are a type of exosome carrying fat and are secreted from mammary epithelial cells by budding (7). They are produced by the lactating epithelial cells that line the lumens of the mammary gland.…”

Section: Discussionmentioning

confidence: 99%

“…At the initial stage of involution, these apoptotic cells are thought to be engulfed mainly by neighboring epithelial cells; in the later stage, they seem to be cleared by macrophages that migrate into the gland (3,6). Milk fat globules (MFGs) are minute globules carrying fat that are secreted from the epithelial cells into the lumen during lactation (7). Upon weaning, many MFGs remain in the lumen, and they seem to be engulfed by epithelial cells lining the lobules in the mammary gland (8).…”

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confidence: 99%

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Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Hanayama

Nagata

2005

Proc. Natl. Acad. Sci. U.S.A.

120

118

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During the involution of mammary glands, epithelial cells undergo apoptosis and are cleared for the next cycle of lactation. The clearance of apoptotic epithelial cells is mediated by neighboring epithelial cells and by macrophages that migrate into the mammary glands. Here, we report that milk fat globule EGF factor 8 (MFG-E8), a secreted glycoprotein that binds to apoptotic cells by recognizing phosphatidylserine, was expressed by epithelial cells and macrophages in mammary glands and was involved in engulfment of apoptotic cells. A deficiency of MFG-E8 caused the accumulation of a large number of milk fat globules (MFGs) in the mammary ducts during involution, indicating that the excess MFGs were cleared by an MFG-E8-dependent mechanism. The MFG-E8 ؊/؊ mice developed mammary duct ectasia with periductal mastitis, and the redevelopment of the mammary gland for their second litter was impaired. These results demonstrate that MFG-E8-mediated phagocytosis of apoptotic epithelial cells and MFGs is important for efficient involution of mammary glands.exosomes ͉ mastitis ͉ phosphatidylserine M ammary glands are unique mammalian organs that are developed to nurse offspring. For each pregnancy, the glands undergo a cycle of development, lactation, and involution. In each cycle, mammalian epithelial cells proliferate, differentiate, and die. The involution of mammary glands is triggered when the suckling stimulus is lost, usually upon weaning, and milk accumulates in the glands. The involution takes Ϸ10 days in mice and can be divided into two phases (1-3). In the first phase, which is reversible and lasts 48 h after weaning, mammary epithelial cells lose their differentiated function. In the second phase, the basement membranes and extracellular matrix in the mammary glands are degraded by proteases, leading to destruction of the lobular-alveolar architecture of the mammary glands. As involution progresses, mammary epithelial cells are removed and adipocytes concomitantly reappear, and the lobular-alveolar structure is reorganized to approach that of virgin glands (4).During the involution process, epithelial cells undergo apoptosis and are shed into the lumen (5). At the initial stage of involution, these apoptotic cells are thought to be engulfed mainly by neighboring epithelial cells; in the later stage, they seem to be cleared by macrophages that migrate into the gland (3, 6). Milk fat globules (MFGs) are minute globules carrying fat that are secreted from the epithelial cells into the lumen during lactation (7). Upon weaning, many MFGs remain in the lumen, and they seem to be engulfed by epithelial cells lining the lobules in the mammary gland (8). How these epithelial cells and macrophages recognize and engulf apoptotic cells and MFGs has not been well elucidated.Many molecules expressed on the surface of apoptotic cells or phagocytes have been proposed as ligands and receptors for the engulfment of apoptotic cells (9 -11). Mouse MFG EGF factor 8 (MFG-E8), called lactadherin in humans, is a 72-kDa glycoprotein s...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Hanayama

Nagata

2005

Proc. Natl. Acad. Sci. U.S.A.

120

118

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“…All of these parameters were similar in Mfge8 +/+ and Mfge8 / brains. Thus, the brain serine (PS), which can be recognized by the secreted ligand, Mfge8 (milk fat globule epidermal growth factor 8; Patton and Keenan, 1975). By virtue of its affinity to PS, Mfge8 helps mediating the removal of apoptotic bodies (Hanayama et al, 2002).…”

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confidence: 99%

Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner

Kranich¹,

Kräutler²,

Falsig³

et al. 2010

J Cell Biol

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Progressive accumulation of PrP(Sc), a hallmark of prion diseases, occurs when conversion of PrP(C) into PrP(Sc) is faster than PrP(Sc) clearance. Engulfment of apoptotic bodies by phagocytes is mediated by Mfge8 (milk fat globule epidermal growth factor 8). In this study, we show that brain Mfge8 is primarily produced by astrocytes. Mfge8 ablation induced accelerated prion disease and reduced clearance of cerebellar apoptotic bodies in vivo, as well as excessive PrP(Sc) accumulation and increased prion titers in prion-infected C57BL/6 × 129Sv mice and organotypic cerebellar slices derived therefrom. These phenotypes correlated with the presence of 129Sv genomic markers in hybrid mice and were not observed in inbred C57BL/6 Mfge8(-/-) mice, suggesting the existence of additional strain-specific genetic modifiers. Because Mfge8 receptors are expressed by microglia and depletion of microglia increases PrP(Sc) accumulation in organotypic cerebellar slices, we conclude that engulfment of apoptotic bodies by microglia may be an important pathway of prion clearance controlled by astrocyte-borne Mfge8.

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“…They contain mainly triacylglycerols and sterols. The intracellular precursors of milk fat globules, milk secretory granules, arise as milk lipids inundate between the leaflets of the endoplasmic reticulum (ER) membrane, distending the leaflet facing the cytoplasm and causing primary droplets of accumulated lipid to bud off the ER (1,(3)(4)(5)(6). Milk secretory granules arise by the fusion of primary lipid droplets and are thus enveloped in a monolayer of phospholipids from the cytoplasmic leaflet of the ER membrane, as are all other lipid droplets (7)(8)(9)(10)(11)(12)(13)(14)(15).…”

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confidence: 99%

Butyrophilin controls milk fat globule secretion

Robenek

Hofnagel

Buers

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

130

124

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The molecular mechanism underlying milk fat globule secretion in mammary epithelial cells ostensibly involves the formation of complexes between plasma membrane butyrophilin and cytosolic xanthine oxidoreductase. These complexes bind adipophilin in the phospholipid monolayer of milk secretory granules, the precursors of milk fat globules, enveloping the nascent fat globules in a layer of plasma membrane and pinching them off the cell. However, using freeze-fracture immunocytochemistry, we find these proteins in locations other than those previously inferred. Significantly, butyrophilin in the residual plasma membrane of the fat globule envelope is concentrated in a network of ridges that are tightly apposed to the monolayer derived from the secretory granule, and the ridges coincide with butyrophilin labeling in the globule monolayer. Therefore, we propose that milk fat globule secretion is controlled by interactions between plasma membrane butyrophilin and butyrophilin in the secretory granule phospholipid monolayer rather than binding of butyrophilin-xanthine oxidoreductase complexes to secretory granule adipophilin.freeze-fracture immunocytochemistry ͉ lipid droplet-associated proteins ͉ mammary epithelial cells ͉ milk secretory granules

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The Milk fat globule membrane

Cited by 364 publications

References 158 publications

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Impaired involution of mammary glands in the absence of milk fat globule EGF factor 8

Engulfment of cerebral apoptotic bodies controls the course of prion disease in a mouse strain–dependent manner

Butyrophilin controls milk fat globule secretion

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