Butyrophilin controls milk fat globule secretion

Robenek, Horst; Hofnagel, Oliver; Buers, Insa; Lorkowski, Stefan; Schnoor, Michael; Robenek, Mirko J.; Heid, Hans; Troyer, David; Severs, Nicholas J.

doi:10.1073/pnas.0600795103

Cited by 131 publications

(134 citation statements)

References 48 publications

Supporting

Mentioning

125

Contrasting

Order By: Relevance

“…The droplets grow during their migration to the apical pole of the cell due to the continuation of the synthesis of lipids (Ollivier-Bousquet, 2002;Heid and Keenan, 2005;McManaman et al, 2007). The secretion would correspond to the membrane enwrapping the CLD and its secretion in association with the exocytosis of the golgiderived secretory vesicles containing caseins micelles (Wu et al, 2000;Keenan and Mather, 2006;Robenek et al, 2006;McManaman et al, 2007;Truchet et al, 2014). According to Heid and Keenan (2005), these mechanisms should be regulated but the regulation processes remain hypothetic.…”

Section: Introductionmentioning

confidence: 99%

Relationships between milks differentiated on native milk fat globule characteristics and fat, protein and calcium compositions

Couvreur

Hurtaud

2017

Animal

View full text Add to dashboard Cite

Many studies have shown that milk fat globule (MFG) diameter varies in dairy cows in relation to diet and/or breed. However, the mechanisms governing the size of the fat globules remain hypothetical. Our objective was to determine the variable biochemical characteristics (fat, protein, fatty acids (FA), casein and calcium (Ca) contents) between individual milk which differed in both MFG diameter and membrane content, in order to speculate about the links between milk synthesis and MFG secretion. With this aim, we built five databases of individual milk samples from 21 experiments performed between 2003 and 2011. Three of them grouped data from trials dealing with breed/diet effects and included information about: (i) MFG size/membrane, fat and protein contents (n = 982), (ii) previous parameters plus FA profile (n = 529) and (iii) previous parameters plus true protein composition and calcium contents (n = 101). A hierarchical clustering analysis performed on these three databases yielded four groups differing in the MFG characteristics. We observed significant differences among groups for the following parameters: (i) fat content and fat : protein ratio; (ii) de novo and polyunsaturated FA contents; (iii) Ca contents. These relationships could result from potential process regulating the synthesis and secretion of MFG: (i) the apical membrane turnover for MFG secretion and (ii) cytoplasmic lipid droplet formation in the lactocyte during its migration from the basal to the apical pole. The two other databases grouped data from trials dealing with milking frequency (n = 211), milking kinetics and milk type (residual v. cisternal) (n = 224). They were used to study the relationships between the size of the MFG and milk composition for high native fat contents (from 60 up to 100 g/kg in residual milks). We observed curvilinear relationships between the size of the MFG and fat content, as well as with the fat : protein ratio. This result suggests that MFG diameter reaches a threshold but mechanisms are still unknown.

show abstract

Section: Introductionmentioning

confidence: 99%

Relationships between milks differentiated on native milk fat globule characteristics and fat, protein and calcium compositions

Couvreur

Hurtaud

2017

Animal

View full text Add to dashboard Cite

show abstract

“…The molecules comprise three structurally related members, BTN3A1, BTN3A2 and BTN3A3 [2,3]. Structurally, the BTNs are composed of an extracellular IgV-like domain, followed by an IgC-like domain and a heptad repeated sequence [2][3][4][5][6][7]. Some BTNs harbor an intracellular domain of 166 amino acids, named B30.2, presumably involved in intracellular signal transduction, notably the BTN implied in the regulation of superoxide concentrations [8,9].…”

Section: Introductionmentioning

confidence: 99%

Differential role for CD277 as a co‐regulator of the immune signal in T and NK cells

et al. 2011

View full text Add to dashboard Cite

The human butyrophilin (BTN) 3 or CD277 molecules belong to the B7 family members and are expressed in various immune cells such as T and NK cells. Here, we show that CD277 triggering considerably enhances TCR-induced cytokine production and cell proliferation, even when another co-stimulatory molecule, CD28, is engaged. These CD277-induced additive functional effects are in accordance with the detection of early T-cell activation events such as TCR-induced cell signaling being increased upon CD277 engagement. However, we found that CD277 triggering is not involved in CD16-or NKp46-induced NK cell activation. BTN3/CD277 comprises three structurally related members, BTN3A1, BTN3A2 and BTN3A3. CD277 antibodies recognize all isoforms and we describe a differential expression of BTN3 isoforms between T and NK cells that could explain differential CD277 functions between T and NK cells. Our results show that, while T cells express all BTN3/CD277 transcripts, NK cells express mostly BTN3A2, which lacks the B30.2 intracellular domain. Furthermore, NKp30-induced cytokine production is decreased by the specific engagement of BTN3A2, but not by BTN3A1 triggering. Thus, we provide new insights into the CD277 co-stimulatory pathway that may differentially participate in the regulation of various cell-mediated immune responses.

show abstract

“…These data are the primary basis for the current hypothesis that ADPH directly associates with BTN and XOR to achieve CLD secretion (2, 11). However, direct support for this mechanism of CLD secretion is lacking, and alternative mechanisms have been proposed (11,14). Thus, additional studies are required to establish the details by which mammary epithelial cells envelop and secrete CLD.…”

mentioning

confidence: 99%

The Adipophilin C Terminus Is a Self-folding Membrane-binding Domain That Is Important for Milk Lipid Secretion

Chong

Russell

Schaack

et al. 2011

Journal of Biological Chemistry

View full text Add to dashboard Cite

Cytoplasmic lipid droplets (CLD) in mammary epithelial cells undergo secretion by a unique membrane envelopment process to produce milk lipids. Adipophilin (ADPH/Plin2), a member of the perilipin/PAT family of lipid droplet-associated proteins, is hypothesized to mediate CLD secretion through interactions with apical plasma membrane elements. We found that the secretion of CLD coated by truncated ADPH lacking the C-terminal region encoding a putative four-helix bundle structure was impaired relative to that of CLD coated by full-length ADPH. We used homology modeling and analyses of the solution and membrane binding properties of purified recombinant ADPH C terminus to understand how this region possibly mediates CLD secretion. Homology modeling supports the concept that the ADPH C terminus forms a four-helix bundle motif and suggests that this structure can form stable membrane bilayer interactions. Circular dichroism and protease mapping studies confirmed that the ADPH C terminus is an independently folding ␣-helical structure that is relatively resistant to urea denaturation. Liposome binding studies showed that the purified C terminus binds to phospholipid membranes through electrostatic dependent interactions, and cell culture studies documented that it localizes to the plasma membrane. Collectively, these data provide direct evidence that the ADPH C terminus forms a stable membrane binding helical structure that is important for CLD secretion. We speculate that interactions between the four-helix bundle of ADPH and membrane phospholipids may be an initial step in milk lipid secretion.Milk lipids are an essential source of neonatal calories and provide nutrients in the form of fatty acids and bioactive lipids that are required for growth and development (1). Milk lipids are delivered to the newborn as milk fat globules (MFG) 4 derived from triglyceride-rich cytoplasmic lipid droplets (CLD) (2). Adipophilin (ADPH/ADRP/Adfp/Plin2), a member of the perilipin/PAT (perilipin/adipophilin/TIP47) family of proteins (3), is an abundant MFG protein (4 -6) and a prominent CLDassociated protein of mammary epithelial cells (7,8). PAT proteins have been shown to promote the formation and accumulation of CLD in a variety of tissues (9, 10) and are also implicated in the trafficking and secretion of CLD (2, 9). The lactating mammary gland is an ideal system to study the recurrent cycles of CLD formation, accumulation, and secretion, and previous work from our laboratory has implicated ADPH in each of these processes (5,8,11).CLD are secreted during lactation by an apocrine process where the apical plasma membrane engulfs associated CLD, which are then released by a budding process to form MFG (2). Two key regulators of CLD secretion are the transmembrane protein butyrophilin (BTN) and the cytoplasmic homodimer, xanthine oxidoreductase (XOR). Mice deficient in either of these proteins display impaired CLD envelopment and secretion (12, 13). In addition to being an abundant protein on mammary epithelial CLD and secreted MFG ...

show abstract

Butyrophilin controls milk fat globule secretion

Cited by 131 publications

References 48 publications

Relationships between milks differentiated on native milk fat globule characteristics and fat, protein and calcium compositions

Relationships between milks differentiated on native milk fat globule characteristics and fat, protein and calcium compositions

Differential role for CD277 as a co‐regulator of the immune signal in T and NK cells

The Adipophilin C Terminus Is a Self-folding Membrane-binding Domain That Is Important for Milk Lipid Secretion

Contact Info

Product

Resources

About