Lipocalin 1 Explained

Lipocalin-1 is a protein that in humans is encoded by the LCN1 gene.^{[1] [2]}

The protein encoded by this gene belongs to the lipocalin family. Lipocalins are a group of extracellular proteins that are able to bind lipophiles by enclosure within their structures to minimize solvent contact. This protein may bind hydrophobic ligands and inhibit cysteine proteinases. It may also play a role in taste reception.

Structure

Proteins are classified into the lipocalin family by their 8 antiparallel beta-sheets that form a barrel structure which acts as the binding site for ligands.

Function

Lipocalin-1 (LCN1) is capable of binding a wide variety of lipophilic molecules along with zinc and chloride ions. Because of this feature, LCN1’s main function is thought to be the removal of potentially harmful lipids and lipophilic molecules from the body by binding them. The LCN1-Ligand complex is then imported via Lipocalin-1-Interacting Membrane Receptor (LIMR) so the bound molecule can be broken down safely within the cell.^[3] This process of retrieving molecules may impact several processes including pheromone signaling, immunodulation, inflammation, detoxification, tissue development, apoptosis and more.

LCN1 shares three sequence motifs with cystatins which enables LCN1 to act in a similar manner to cystatins as a cysteine proteinase inhibitor. These domains have specifically been shown to bind Papain.^{[4] [5]}

LCN1 also plays a role in stabilizing the lipid layer of the tear film, though the details of this are not yet well understood.^{[6] [7]}

History

Lipocalin-1 was initially thought to be produced exclusively by exocrine glands but has also been found in corticotrophs of the pituitary gland.^[8]

Alternate Names: Human Tear Prealbumin, Tear Lipocalin, von Ebner’s Gland Protein

Clinical

When a cell is under stress, due to inflammation, infection, or otherwise, it will produce elevated levels of lipocalin-1 (LCN1). This makes it a potential noninvasive biomarker for various diseases. This potential has been shown in a study of IVF blastocysts, where elevated levels of LCN1 indicated aneuploidy in the blastocyst.^[9]

Further reading

• Book: Glasgow BJ, Abduragimov AR, Gasymov OK, Yusifov TN . Tear Lipocalin: Structure, Function and Molecular Mechanisms of Action . Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3 . 506 . Pt A . 555–65 . 12613960 . 10.1007/978-1-4615-0717-8_78 . 978-1-4613-5208-2 . Advances in Experimental Medicine and Biology . 2002 .
• Redl B, Holzfeind P, Lottspeich F . cDNA cloning and sequencing reveals human tear prealbumin to be a member of the lipophilic-ligand carrier protein superfamily . The Journal of Biological Chemistry . 267 . 28 . 20282–7 . October 1992 . 10.1016/S0021-9258(19)88698-2 . 1400345 . free .
• Lassagne H, Nguyen VC, Mattei MG, Gachon AM . Assignment of LCN1 to human chromosome 9 is confirmed . Cytogenetics and Cell Genetics . 71 . 1 . 104 . 1995 . 7606920 . 10.1159/000134073 . free .
• Bläker M, Kock K, Ahlers C, Buck F, Schmale H . Molecular cloning of human von Ebner's gland protein, a member of the lipocalin superfamily highly expressed in lingual salivary glands . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1172 . 1–2 . 131–7 . February 1993 . 7679926 . 10.1016/0167-4781(93)90279-m .
• Holzfeind P, Redl B . Structural organization of the gene encoding the human lipocalin tear prealbumin and synthesis of the recombinant protein in Escherichia coli . Gene . 139 . 2 . 177–83 . February 1994 . 8112601 . 10.1016/0378-1119(94)90752-8 .
• Lassagne H, Gachon AM . Cloning of a human lacrimal lipocalin secreted in tears . Experimental Eye Research . 56 . 5 . 605–9 . May 1993 . 8500570 . 10.1006/exer.1993.1075 .
• Holzfeind P, Merschak P, Rogatsch H, Culig Z, Feichtinger H, Klocker H, Redl B . Expression of the gene for tear lipocalin/von Ebner's gland protein in human prostate . FEBS Letters . 395 . 2–3 . 95–8 . October 1996 . 8898072 . 10.1016/0014-5793(96)01008-3 . 22843813 . free .
• van't Hof W, Blankenvoorde MF, Veerman EC, Amerongen AV . The salivary lipocalin von Ebner's gland protein is a cysteine proteinase inhibitor . The Journal of Biological Chemistry . 272 . 3 . 1837–41 . January 1997 . 8999869 . 10.1074/jbc.272.3.1837 . free .
• Redl B, Wojnar P, Ellemunter H, Feichtinger H . Identification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis . Laboratory Investigation; A Journal of Technical Methods and Pathology . 78 . 9 . 1121–9 . September 1998 . 9759656 .
• Gasymov OK, Abduragimov AR, Yusifov TN, Glasgow BJ . Interaction of tear lipocalin with lysozyme and lactoferrin . Biochemical and Biophysical Research Communications . 265 . 2 . 322–5 . November 1999 . 10558865 . 10.1006/bbrc.1999.1668 .
• Wojnar P, Lechner M, Merschak P, Redl B . Molecular cloning of a novel lipocalin-1 interacting human cell membrane receptor using phage display . The Journal of Biological Chemistry . 276 . 23 . 20206–12 . June 2001 . 11287427 . 10.1074/jbc.M101762200 . free .
• Wojnar P, van't Hof W, Merschak P, Lechner M, Redl B . The N-terminal part of recombinant human tear lipocalin/von Ebner's gland protein confers cysteine proteinase inhibition depending on the presence of the entire cystatin-like sequence motifs . Biological Chemistry . 382 . 10 . 1515–20 . October 2001 . 11727836 . 10.1515/BC.2001.186 . 44411516 .
• Wojnar P, Dirnhofer S, Ladurner P, Berger P, Redl B . Human lipocalin-1, a physiological scavenger of lipophilic compounds, is produced by corticotrophs of the pituitary gland . The Journal of Histochemistry and Cytochemistry . 50 . 3 . 433–5 . March 2002 . 11850445 . 10.1177/002215540205000314 . free .
• Wojnar P, Lechner M, Redl B . Antisense down-regulation of lipocalin-interacting membrane receptor expression inhibits cellular internalization of lipocalin-1 in human NT2 cells . The Journal of Biological Chemistry . 278 . 18 . 16209–15 . May 2003 . 12591932 . 10.1074/jbc.M210922200 . free .
• Book: Glasgow BJ, Abduragimov AR, Gassymov OK, Yusifov TN, Ruth EC, Faull KF . Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3 . Vitamin e Associated with the Lipocalin Fraction of Human Tears . Advances in Experimental Medicine and Biology . 2002 . 506 . Pt A . 567–72 . 12613961 . 10.1007/978-1-4615-0717-8_79 . 978-1-4613-5208-2 .
• Book: Tiffany JM, Nagyová B . The Role of Lipocalin in Determining the Physical Properties of Tears . Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3 . 506 . Pt A . 581–5 . 12613963 . 10.1007/978-1-4615-0717-8_81 . 978-1-4613-5208-2 . Advances in Experimental Medicine and Biology . 2002 .
• Gasymov OK, Abduragimov AR, Yusifov TN, Glasgow BJ . Interstrand loops CD and EF act as pH-dependent gates to regulate fatty acid ligand binding in tear lipocalin . Biochemistry . 43 . 40 . 12894–904 . October 2004 . 15461462 . 10.1021/bi049076o .

Notes and References

1. Lassagne H, Ressot C, Mattei MG, Gachon AM . Assignment of the human tear lipocalin gene (LCN1) to 9q34 by in situ hybridization . Genomics . 18 . 1 . 160–1 . October 1993 . 8276406 . 10.1006/geno.1993.1444 .
2. Web site: Entrez Gene: LCN1 lipocalin 1 (tear prealbumin).
3. Wojnar P, Lechner M, Redl B . Antisense down-regulation of lipocalin-interacting membrane receptor expression inhibits cellular internalization of lipocalin-1 in human NT2 cells . The Journal of Biological Chemistry . 278 . 18 . 16209–15 . May 2003 . 12591932 . 10.1074/jbc.M210922200 . 24433456 . free .
4. van't Hof W, Blankenvoorde MF, Veerman EC, Amerongen AV . The salivary lipocalin von Ebner's gland protein is a cysteine proteinase inhibitor . The Journal of Biological Chemistry . 272 . 3 . 1837–41 . January 1997 . 8999869 . 10.1074/jbc.272.3.1837 . 2650128 . free .
5. Wojnar P, van't Hof W, Merschak P, Lechner M, Redl B . The N-terminal part of recombinant human tear lipocalin/von Ebner's gland protein confers cysteine proteinase inhibition depending on the presence of the entire cystatin-like sequence motifs . Biological Chemistry . 382 . 10 . 1515–20 . October 2001 . 11727836 . 10.1515/BC.2001.186 . 44411516 .
6. Nagyová B, Tiffany JM . Components responsible for the surface tension of human tears . Current Eye Research . 19 . 1 . 4–11 . July 1999 . 10415451 . 10.1076/ceyr.19.1.4.5341 .
7. Saaren-Seppälä H, Jauhiainen M, Tervo TM, Redl B, Kinnunen PK, Holopainen JM . Interaction of purified tear lipocalin with lipid membranes . Investigative Ophthalmology & Visual Science . 46 . 10 . 3649–56 . October 2005 . 16186346 . 10.1167/iovs.05-0176 .
8. Wojnar P, Dirnhofer S, Ladurner P, Berger P, Redl B . Human lipocalin-1, a physiological scavenger of lipophilic compounds, is produced by corticotrophs of the pituitary gland . The Journal of Histochemistry and Cytochemistry . 50 . 3 . 433–5 . March 2002 . 11850445 . 10.1177/002215540205000314 . 26078329 . free .
9. McReynolds S, Vanderlinden L, Stevens J, Hansen K, Schoolcraft WB, Katz-Jaffe MG . Lipocalin-1: a potential marker for noninvasive aneuploidy screening . Fertility and Sterility . 95 . 8 . 2631–3 . June 2011 . 21324447 . 10.1016/j.fertnstert.2011.01.141 . free .