Freeze-fracture observations of the lactating rat mammary gland. Membrane events during milk fat secretion.

Menezes, A.Peixoto De; Silva, P Pinto da

doi:10.1083/jcb.76.3.767

Cited by 47 publications

(12 citation statements)

References 27 publications

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“…These data parallel the results of freeze-fracture electron microscopy from several laboratories which show that the fracture faces of MFGM are depleted of the intramembranous particles typically associated with integral proteins (27)(28)(29).…”

supporting

confidence: 87%

“…The results are at variance with some freeze-fracture studies which showed that MFGM and areas of the apical plasma membrane in close apposition with budding fat droplets are depleted of the intramembranous particles associated with integral membrane proteins (27)(28)(29). Since BTN comprises 20 -40% of the protein content of bovine MFGM (47,48), as an integral protein, it would be expected to give rise to identifiable particles on the fractured membrane halves.…”

Section: Discussioncontrasting

confidence: 55%

“…Since BTN comprises 20 -40% of the protein content of bovine MFGM (47,48), as an integral protein, it would be expected to give rise to identifiable particles on the fractured membrane halves. The apparent lack of intramembranous particles was taken as evidence that the protein components of MFGM including BTN undergo extensive rearrangement and exclusion from the membrane lipid bilayer during the budding and secretion of fat droplets (27,28). However, in some studies, intra-membranous particles have been identified in freeze-fractured preparations of MFGM, albeit sometimes at lower densities and in clusters, compared with the apical plasma membrane (29,49).…”

Section: Discussionmentioning

confidence: 99%

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Butyrophilin Is Expressed in Mammary Epithelial Cells from a Single-sized Messenger RNA as a Type I Membrane Glycoprotein

Banghart¹,

Chamberlain²,

Velarde³

et al. 1998

Journal of Biological Chemistry

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We investigated the expression of butyrophilin in eukaryotic cells with a view to determining the number of mRNA species, the incorporation of the peptide chain into microsomes, and the topology of the processed protein in biological membranes. Butyrophilin is synthesized from a single sized mRNA in both bovine and murine lactating mammary tissue and associates with microsomal membranes with a type I topology (N exo ⅐C cyto ) via a single hydrophobic anchor in the middle of the sequence. Several isoelectric variants of the protein were detected in cellular membranes from lactating bovine mammary tissue and in the milk-fat-globule membrane. We found no evidence for soluble forms of butyrophilin in postmicrosomal supernatants. The 66-kDa protein appears to be subjected to limited proteolysis, giving rise to a 62-kDa fragment lacking the C terminus and to other more minor fragments of lower M r in the milk-fat-globule membrane. Antipeptide antibodies to epitopes within the N-and C-terminal domains were used to show that butyrophilin retains a type I topology in plasma membranes when expressed in insect cells from a baculovirus vector, and in secreted milk-fat globules. These data do not agree with previous suggestions that butyrophilin may exist in cytoplasmic soluble forms, or be reorganized in the plane of the lipid bilayer during secretion in lipid droplets from mammary cells. The results are discussed with reference to the role butyrophilin may play as the principal scaffold for the assembly of a complex with xanthine oxidase and other proteins that functions in the budding and release of milk-fat globules from the apical surface during lactation.Several years ago we cloned a cDNA encoding the major milk-fat-globule membrane (MFGM) 1 protein, butyrophilin (BTN) (1) with a view to understanding the function of this mammary-specific protein in milk-fat secretion (for reviews of this process, see Refs. 2-4). From the derived amino acid sequence we predicted that BTN is an integral protein with a single membrane anchor and a glycosylated exoplasmic N terminus (type I orientation) (1). Subsequent comparisons with more recently cloned cDNAs have established that BTN is a member of the immunoglobulin superfamily (5) with two Nterminal immunoglobulin domains, one of the intermediate type (IgI) (6) toward the N terminus and one of the constant C1 type (7) toward the membrane bilayer (8). A large proportion of the C-terminal region comprises the RFP or B30.2 domain, a sequence which is present in a subfamily of zinc-finger proteins (9, 10), and a group of recently identified BTN-like genes (11, 12). Several workers have proposed that BTN may function as an integral receptor for cytoplasmic fat droplets and that budding of the droplets at the cell surface is initiated by interactions between the cytoplasmic tail of BTN and other proteins, notably the redox enzyme xanthine oxidase (1, 13-16). However, the assumption that BTN behaves as an integral protein in mammary epithelial cells has been confounded by several observati...

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supporting

confidence: 87%

Section: Discussioncontrasting

confidence: 55%

Section: Discussionmentioning

confidence: 99%

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Butyrophilin Is Expressed in Mammary Epithelial Cells from a Single-sized Messenger RNA as a Type I Membrane Glycoprotein

Banghart¹,

Chamberlain²,

Velarde³

et al. 1998

Journal of Biological Chemistry

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“…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). However, in contrast to all other lipid droplets, milk secretory granules are transported to the cell surface where they are pinched off into the alveolar space entirely surrounded in a layer of plasma membrane (2,(16)(17)(18).…”

mentioning

confidence: 99%

Butyrophilin controls milk fat globule secretion

Robenek

Hofnagel

Buers

et al. 2006

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

131

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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“…Major differences in protein composition were noted. However, fat globule membrane may not have the same composition as the apical plasma membrane and the secretory vesicle fractions may have been enriched in immature vesicle membranes (Peixoto de Menezes and Pinto da Silva 1978;Mather and Keenan 1983;Mather 1987). Well characterised fractions of apical plasma membrane and mature secretory vesicle membrane will be needed to resolve these issues.…”

Section: Discussionmentioning

confidence: 99%

The distribution of MUC1, an apical membrane glycoprotein, in mammary epithelial cells at the resolution of the electron microscope: implications for the mechanism of milk secretion

Mather

Jack

Madara

et al. 2001

Cell and Tissue Research

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The distribution of the glycoprotein, mucin 1 (MUC1), was determined in lactating guinea-pig mammary tissue at the resolution of the electron microscope. MUC1 was detected on the apical plasma membrane of secretory epithelial cells, the surface of secreted milk-fat globules, the limiting membranes of secretory vesicles containing casein micelles and in small vesicles and tubules in the apical cytoplasm. Some of the small MUC1-containing vesicles were associated with the surfaces of secretory vesicles and fat droplets in the cytoplasm. MUC1 was detected in much lower amounts on basal and lateral plasma membranes. By quantitative immunocytochemistry, the ratio of MUC1 on apical membranes and milk-fat globules to that on secretory vesicle membranes was estimated to be 9.2:1 (density of colloidal gold particles/microm membrane length). The ratio of MUC1 on apical membranes compared with basal/lateral membranes was approximately 99:1. The data are consistent with a mechanism for milk-fat secretion in which lipid globules acquire an envelope of membrane from the apical surface and possibly from small vesicles containing MUC1 in the cytoplasm. During established lactation, secretory vesicle membrane does not appear to contribute substantially to the milk-fat globule membrane, or to give rise in toto to the apical plasma membrane.

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Freeze-fracture observations of the lactating rat mammary gland. Membrane events during milk fat secretion.

Cited by 47 publications

References 27 publications

Butyrophilin Is Expressed in Mammary Epithelial Cells from a Single-sized Messenger RNA as a Type I Membrane Glycoprotein

Butyrophilin Is Expressed in Mammary Epithelial Cells from a Single-sized Messenger RNA as a Type I Membrane Glycoprotein

Butyrophilin controls milk fat globule secretion

The distribution of MUC1, an apical membrane glycoprotein, in mammary epithelial cells at the resolution of the electron microscope: implications for the mechanism of milk secretion

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