MFGE8 explained

Milk fat globule-EGF factor 8 protein (Mfge8), also known as lactadherin, is a protein that in humans is encoded by the MFGE8 gene.^{[1] [2]}

Species distribution

Mfge8 is a secreted protein found in vertebrates, including mammals as well as birds.

Function

MFGE8 may function as a cell adhesion protein to connect smooth muscle to elastic fibers in arteries.^[3] An amyloid fragment of MFGE8 known as medin accumulates in the aorta with aging.^[4] MFGE8 in the vasculature of adults can induce recovery from ischemia by facilitating angiogenesis.^[5] It has been suggested that antagonizing MFGE8-induced angiogenesis could be a way of fighting cancer.^[6]

MFGE8 contains a phosphatidylserine (PS) binding domain, as well as an arginine-glycine-aspartic acid motif, which enables the binding to integrins. MFGE8 binds PS, which is exposed on the surface of apoptotic cells.^[7] Opsonization of the apoptotic cells and binding to integrins on the surface of phagocytic cells, mediates the engulfment of the dead cell.

Further reading

• Book: Peterson JA, Scallan CD, Ceriani RL, Hamosh M . Structural and Functional Aspects of Three Major Glycoproteins of the Human Milk Fat Globule Membrane . Bioactive Components of Human Milk . Advances in Experimental Medicine and Biology . 501 . 179–87 . 2002 . 11787681 . 10.1007/978-1-4615-1371-1_23. 978-1-4613-5521-2 .
• Larocca D, Peterson JA, Urrea R, etal . A Mr 46,000 human milk fat globule protein that is highly expressed in human breast tumors contains factor VIII-like domains. . Cancer Res. . 51 . 18 . 4994–8 . 1991 . 1909932 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. . Gene . 138 . 1–2 . 171–4 . 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Couto JR, Taylor MR, Godwin SG, etal . Cloning and sequence analysis of human breast epithelial antigen BA46 reveals an RGD cell adhesion sequence presented on an epidermal growth factor-like domain. . DNA Cell Biol. . 15 . 4 . 281–6 . 1996 . 8639264 . 10.1089/dna.1996.15.281 .
• Collins C, Nehlin JO, Stubbs JD, etal . Mapping of a newly discovered human gene homologous to the apoptosis associated-murine mammary protein, MFG-E8, to chromosome 15q25. . Genomics . 39 . 1 . 117–8 . 1997 . 9027496 . 10.1006/geno.1996.4425 .
• Aoki N, Ishii T, Ohira S, etal . Stage specific expression of milk fat globule membrane glycoproteins in mouse mammary gland: comparison of MFG-E8, butyrophilin, and CD36 with a major milk protein, beta-casein. . Biochim. Biophys. Acta . 1334 . 2–3 . 182–90 . 1997 . 9101712 . 10.1016/s0304-4165(96)00091-8.
• Taylor MR, Couto JR, Scallan CD, etal . Lactadherin (formerly BA46), a membrane-associated glycoprotein expressed in human milk and breast carcinomas, promotes Arg-Gly-Asp (RGD)-dependent cell adhesion. . DNA Cell Biol. . 16 . 7 . 861–9 . 1997 . 9260929 . 10.1089/dna.1997.16.861 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, etal . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. . Gene . 200 . 1–2 . 149–56 . 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Giuffrida MG, Cavaletto M, Giunta C, etal . Isolation and characterization of full and truncated forms of human breast carcinoma protein BA46 from human milk fat globule membranes. . J. Protein Chem. . 17 . 2 . 143–8 . 1998 . 9535276 . 10.1023/A:1022531500370 . 36987464 .
• Newburg DS, Peterson JA, Ruiz-Palacios GM, etal . Role of human-milk lactadherin in protection against symptomatic rotavirus infection. . Lancet . 351 . 9110 . 1160–4 . 1998 . 9643686 . 10.1016/S0140-6736(97)10322-1 . 25702042 .
• Peterson JA, Hamosh M, Scallan CD, etal . Milk fat globule glycoproteins in human milk and in gastric aspirates of mother's milk-fed preterm infants. . Pediatr. Res. . 44 . 4 . 499–506 . 1998 . 9773837 . 10.1203/00006450-199810000-00006 . free .
• Häggqvist B, Näslund J, Sletten K, etal . Medin: an integral fragment of aortic smooth muscle cell-produced lactadherin forms the most common human amyloid. . Proc. Natl. Acad. Sci. U.S.A. . 96 . 15 . 8669–74 . 1999 . 10411933 . 10.1073/pnas.96.15.8669 . 17574 . 1999PNAS...96.8669H . free .
• Oshima K, Aoki N, Kato T, etal . Secretion of a peripheral membrane protein, MFG-E8, as a complex with membrane vesicles. . Eur. J. Biochem. . 269 . 4 . 1209–18 . 2002 . 11856354 . 10.1046/j.1432-1033.2002.02758.x . free .
• Hanayama R, Tanaka M, Miwa K, etal . Identification of a factor that links apoptotic cells to phagocytes. . Nature . 417 . 6885 . 182–7 . 2002 . 12000961 . 10.1038/417182a . 2002Natur.417..182H . 4429707 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2003 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Lee SH, Seo GS, Park PH, etal . Increased expression of O-acetyl disialoganglioside synthase during rat liver fibrogenesis relates to stellate cell activation. . Biochem. Biophys. Res. Commun. . 303 . 3 . 954–61 . 2003 . 12670504 . 10.1016/S0006-291X(03)00448-0 .
• Rehman KS, Yin S, Mayhew BA, etal . Human myometrial adaptation to pregnancy: cDNA microarray gene expression profiling of myometrium from non-pregnant and pregnant women. . Mol. Hum. Reprod. . 9 . 11 . 681–700 . 2004 . 14561811 . 10.1093/molehr/gag078 . free .
• Ota T, Suzuki Y, Nishikawa T, etal . Complete sequencing and characterization of 21,243 full-length human cDNAs. . Nat. Genet. . 36 . 1 . 40–5 . 2004 . 14702039 . 10.1038/ng1285 . free .
• Reches M, Gazit E . Amyloidogenic hexapeptide fragment of medin: homology to functional islet amyloid polypeptide fragments. . Amyloid . 11 . 2 . 81–9 . 2005 . 15478463 . 10.1080/13506120412331272287 . 22673832 .

Notes and References

1. Web site: Entrez Gene: MFGE8 milk fat globule-EGF factor 8 protein.
2. Collins C, Nehlin JO, Stubbs JD, Kowbel D, Kuo WL, Parry G . Mapping of a newly discovered human gene homologous to the apoptosis associated-murine mammary protein, MFG-E8, to chromosome 15q25 . Genomics . 39 . 1 . 117–8 . January 1997 . 9027496 . 10.1006/geno.1996.4425 .
3. Larsson A, Peng S, Persson H, Rosenbloom J, Abrams WR, Wassberg E, Thelin S, Sletten K, Gerwins P, Westermark P . Lactadherin binds to elastin--a starting point for medin amyloid formation? . Amyloid . 13 . 2 . 78–85 . June 2006 . 16911961 . 10.1080/13506120600722530 . 22755686 .
4. Peng S, Glennert J, Westermark P . Medin-amyloid: a recently characterized age-associated arterial amyloid form affects mainly arteries in the upper part of the body . Amyloid . 12 . 2 . 96–102 . June 2005 . 16011985 . 10.1080/13506120500107006 . 23351552 .
5. Silvestre JS, Théry C, Hamard G, Boddaert J, Aguilar B, Delcayre A, Houbron C, Tamarat R, Blanc-Brude O, Heeneman S, Clergue M, Duriez M, Merval R, Lévy B, Tedgui A, Amigorena S, Mallat Z . Lactadherin promotes VEGF-dependent neovascularization . Nat. Med. . 11 . 5 . 499–506 . May 2005 . 15834428 . 10.1038/nm1233 . 9154352 .
6. Raymond A, Ensslin MA, Shur BD . SED1/MFG-E8: a bi-motif protein that orchestrates diverse cellular interactions . J. Cell. Biochem. . 106 . 6 . 957–66 . April 2009 . 19204935 . 2742659 . 10.1002/jcb.22076 .
7. Aguzzi A, Kranich J, Krautler NJ . Follicular dendritic cells: origin, phenotype, and function in health and disease . . 35 . 3 . 105–113 . 2014 . 10.1016/j.it.2013.11.001 . 24315719 .