Skip to main content
SpringerLink
Log in

Tear Lipocalin: Structure, Function and Molecular Mechanisms of Action

  • Chapter
Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 506))

Abstract

Human tear lipocalin (TL), or von Ebner’s gland protein, accounts for about 15–33% of the protein in tears.1–4 TL has been identified in lacrimal gland, von Ebner’s gland, prostate, nasal and tracheal mucosa and skin.5–12 TL was recognized as a member of the lipocalin family when its primary sequence was determined.7,13,14 Lipocalins form a functionally diverse group of proteins with extremely varied amino acid sequences, yet some similar structural properties (Fig. 1). Eight strands (A-H) are arranged in a β-barrel and are joined by loops between the β-strands.15–19 Many of the lipocalins, including TL, are believed to function as dimers.20,21 There are highly conserved regions that are important to ligand affinity and lipocalin stability. Most lipocalins have 1–3 disulfides bonds and one in particular is conserved and may play a role in modulating ligand binding.15,22 A completely conserved tryptophan on the A strand is implicated in ligand binding and prevention of oxidation of retinol, as well as protein stability of various lipocalins.23,24

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 259.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 329.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 329.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. R.J. Fullard. Identification of proteins in small tear volumes with and without size exclusion HPLC fractionation. Curr. Eye Res. 7:163–179 (1988).

    Article  CAS  PubMed  Google Scholar 

  2. A.M. Gachon, and R.J. Dastugue. Human tears, normal protein pattern and individual protein determination in adults. Curr. Eye Res. 2:301–308 (1983)

    Article  CAS  Google Scholar 

  3. A. Delaire, H. Lassagne, and A.M. Gachon. New members of the lipocalin family in human tear fluid. Exp. Eye Res. 55: 645–647 (1992).

    Article  CAS  PubMed  Google Scholar 

  4. R.J. Fullard, D.M. Kissner. Purification of the isoforms of tear specific prealbumin. Curr. Eye Res. 10:613–628 (1991).

    Article  CAS  PubMed  Google Scholar 

  5. K. Inada. Studies of human tear proteins. 3. Distribution of specific tear prealbumin in lacrimal glands and other adnexa. Jpn. J. Ophthalmol. 28:315–330 (1984).

    CAS  PubMed  Google Scholar 

  6. B.J. Glasgow. Tissue expression of lipocalins in human lacrimal and von Ebner’s glands: colocalization with lysozyme. Graefe’s Arch. Clin. Exp. Ophthalmol. 233:513–522 (1995).

    Article  CAS  Google Scholar 

  7. B. Redl, P. Holzfeind, and F. Lottspeich. cDNA cloning and sequencing reveals human tear prealbumin to be a member of the lipophilic-ligand carrier protein superfamily. J. Biol. Chem. 267:20282–202877 (1992).

    CAS  PubMed  Google Scholar 

  8. P. Holzfeind, P. Merschak, H. Rogatsch, Z. Culig, H. Feichtinger, H. Klocker, and B. Redl. Expression of the gene for tear lipocalin/von Ebner’s gland protein in human prostate. FEBS Lett. 395:95–98 (1997).

    Article  Google Scholar 

  9. B. Redl, P. Wojnar, H. Ellemunter, and H. Feichtinger. Indentification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis. Lab. Invest. 78:1121–1129(1998).

    CAS  PubMed  Google Scholar 

  10. F. Scalfari, M. Casragna, B. Fattori, I. Andreini, C. Maremmmani, and P. Pelosi. Expression of a lipocalin in human nasal mucosa. Comp. Biochem. Physiol. 118B:819–824 (1998).

    Article  Google Scholar 

  11. B. Fattori, M. Castagna, G. Megna, A. Casani, and P. Pelsosi. Immunohistochemical localization of tear lipocalin in human nasal mucosa. Rhinology 36:101–103 (1998).

    CAS  PubMed  Google Scholar 

  12. E. Lacazette, A.M. Gachon, and G. Pitiot. A novel human odorant-binding protein gene family resulting from genomic duplicons at 9q34: differential expression in the orial and genital spheres. Hum. Mol. Genet. 9:289–301 (2000).

    Article  CAS  PubMed  Google Scholar 

  13. M. Bläker, K. Kock, C. Ahlers, F. Buck, and H. Schmale. Molecular cloning of human von Ebner’s gland protein: a member of the lipocalin superfamily highly expressed in lingual salivary gland. Biochim. Biophys. Acta 1172:131–137 (1993).

    Article  PubMed  Google Scholar 

  14. H. Lassagne, and A.M. Gachon. Cloning of a human lacrimal lipocalin secreted in tears. Exp. Eye Res. 55:605–609(1993).

    Article  Google Scholar 

  15. D.R. Flower. The lipocalin protein family: structure and function. Biochem. J. 18:1–14(1996).

    Article  Google Scholar 

  16. B.Y. Qin, M.C. Bewley, L.K. Creamer, H.M. Baker, E.N. Baker, and G.B. Jameson. Structural basis of the Tanford transition of bovine beta-lactoglobulin. Biochemistry 37:14014–14023 (1998).

    Article  CAS  PubMed  Google Scholar 

  17. M.Z. Papiz, L. Sawyer, E.E. Eliopoulos, A.C. North, J.B. Findlay, R. Sivaprasadarao, T.A. Jones, M.E. Newcomer, and P.J. Kraulis. The structure of beta-lactoglobulin and its similarity to plasma retinol-binding protein. Nature 324:383–385 (1986).

    Article  CAS  PubMed  Google Scholar 

  18. B.Y. Qin, L.K. Creamer, E.N. Baker, and G.B. Jameson. 12-Bromododecanoic acid binds inside the calyx of bovine beta-lactoglobulin. FEBS Lett. 438:272–278 (1998).

    Article  CAS  PubMed  Google Scholar 

  19. S.Y. Wu, M.D. Perez, P. Puyol, and L. Sawyer. Beta-lactoglobulin bends palmitate within its central cavity. J. Biol Chem. 274:170–174 (1999).

    Article  CAS  PubMed  Google Scholar 

  20. O.K. Gasymov, A.R. Abduragimov, T.N. Yusifov, and B.J. Glasgow. Interaction of tear lipocalin with lysozyme and lactoferrin. Biochem. Biophys. Res. Commun. 265:322–325 (1999).

    Article  CAS  PubMed  Google Scholar 

  21. C. Creuzenet, and D. Mangroo. Physico-chemical characterization of human von Ebner’s gland protein expressed in Escherichia coli. Protein Expr. Purif. 14:254–260 (1998).

    Article  CAS  PubMed  Google Scholar 

  22. B.J. Glasgow, A.R. Abduragimov, T.N. Yusifov, O.K. Gasymov, J. Horwitz, W.L Hubbell, and K.F. Faull. A conserved disulfide motif in human tear lipocalins influences ligand binding. Biochemistry 37:2215–2225(1998).

    Article  CAS  PubMed  Google Scholar 

  23. O.K. Gasymov, A.R. Abduragimov, T.N. Yusifov, and B.J. Glasgow. Binding studies in tear lipocalin: the role of the conserved tryptophan in maintaining structure, stability, and ligand affinity. Biochim. Biophys. Acta 1433:307–320 (1999).

    Article  CAS  PubMed  Google Scholar 

  24. Y. Katakura, M. Totsuka, A. Maetani, and S. Kaminogawa. Tryptophan-19 of beta-lactoglobulin, the only residue completely conserved in the lipocalin superfamily, is not essential for binding retinol, but relevant to stabilizing bound retinol and maintaining its structure. Biochim. Biophys. Acta 1207:58–67 (1994).

    Article  CAS  PubMed  Google Scholar 

  25. B.J. Glasgow, A.R. Abduragimov, Z.T. Farahbakhsh, K.F. Faull, and W.L. Hubbell. Tear lipocalins bind a broad array of lipid ligands. Curr. Eye Res. 14:363–372 (1995).

    Article  CAS  PubMed  Google Scholar 

  26. B.J. Glasgow, A.R. Abduragimov, O.K. Gasymov, T.N. Yusifov, E.C. Ruth, and K.F. Faull. Vitamin E associated with the lipocalin fraction of human tears. Third International Conference on the Lacrimal Gland, Tear Film and Dry Eye Syndromes: Basic Science and Clinical Relevance, in press.

    Google Scholar 

  27. B.J. Glasgow, A.R. Abduragimov, T.N. Yusifov, and O.K. Gasymov. Studies of ligand binding and CD analysis with apo- and holo- tear lipocalins. Adv. Exp. Med Biol. 483:105–112 (1998).

    Article  Google Scholar 

  28. H. Schmale, H. Holgreve-Grez, and H. Christiansen. Possible role for salivary gland protein in taste reception indicated by homology to lipophilic-ligand carrier proteins. Nature 343:366–369 (1990).

    Article  CAS  PubMed  Google Scholar 

  29. M.E. Selsted, and R.J. Martinez. Isolation and purification of bactericides from tears. Exp. Eye Res. 34:305–318(1982).

    Article  CAS  PubMed  Google Scholar 

  30. A.S. Josephson, and A. Wald. Enhancement of lysozyme activity by anodal tear protein. Proc. Soc. Exp. Biol. Med. 131:677–679 (1969).

    Article  CAS  PubMed  Google Scholar 

  31. T.N. Yusifov, A.R. Abduragimov, O.K. Gasymov, and B.J. Glasgow. Endonuclease activity in lipocalins. Biochem J. 347:815–919 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. W. van’t Hof, M.F. Blankenvoorde, E.C.I. Veerman, and A.V. Amnerangen. The salivary lipocalin von Ebner’s gland protein is a cysteine proteinase inhibitor. J. Biol. Chem. 272:1837–1841 (1997).

    Article  Google Scholar 

  33. B. Redl, P. Wojnar, H. Ellemunter, and H. Feichtinger. Identification of a lipocalin in mucosal glands of the human tracheobronchial tree and its enhanced secretion in cystic fibrosis. Lab Invest. 78:1121–1129(1998).

    CAS  PubMed  Google Scholar 

  34. B.J. Glasgow, G. Marshall, O.K. Gasymov, A.R. Abduragimov, T.N. Yusifov, and CM. Knobler. Tear lipocalins: potential lipid scavengers for the corneal surface. Invest. Ophthalmol Vis. Sci. 40:3100–3107(1999).

    CAS  PubMed  Google Scholar 

  35. B. Nayová, and J.M. Tiffany. Components responsible for the surface tension in tears. Curr. Eye Res. 19:4–11 (1999).

    Article  Google Scholar 

  36. P.T. Janssen, and O.P. van Bijsterveld. Tear fluid proteins in Sjögren’s syndrome. Scand. J. Rheumatol. 61:224–227(1986).

    CAS  Google Scholar 

  37. R.D. Schoenwald, S. Vidvauns, D.E. Wurster, and C.F. Barfknecht. Tear film stability of protein extracts from dry eye patients administered a sigma agonist. J. Ocul. Pharmacol. Ther. 13:151–161 (1997).

    Article  CAS  PubMed  Google Scholar 

  38. Tiffany JM, Winter N, and Bliss G. Tear film stability and tear surface tension. Curr. Eye Res. 8:507–515(1989).

    Article  CAS  PubMed  Google Scholar 

  39. F.J. Holly. Formation and stability of tear film. Int. Ophthalmol Clin. 13:73–96 (1973).

    Article  CAS  PubMed  Google Scholar 

  40. O.K. Gasymov, A.R. Abduragimov, T.N. Yusifov, and B.J. Glasgow. Structural changes in tear lipocalins with ligand binding. Biochim. Biophys. Acta. 1386:145–156 (1998).

    Article  CAS  PubMed  Google Scholar 

  41. J.C. Pandit, B. Nagyová, J.A. Bron, and J.M. Tiffany. Physical properties of stimulated and unstimulated tears. Exp. Eye Res. 68:247–253 (1998).

    Article  Google Scholar 

  42. F.J. Holly, and M.A. Lemp. Wettability and wetting of corneal epithelium. Exp. Eye Res. 11:239–250 (1971).

    Article  CAS  PubMed  Google Scholar 

  43. M. Prats, J. Teissié, and J.F. Tocanne. Lateral proton conduction at lipid-water interfaces and its implications for the chemiosmotic-coupling hypothesis. Nature 322:756–758 (1986).

    Article  CAS  Google Scholar 

  44. B. Redl, P. Merschak, B. Abt, and P. Wojnar. Phage display reveals a novel interaction of human tear lipocalin and thioredoxin which is relevant for ligand binding. FEBS Lett. 460: 182–186 (1999).

    Article  CAS  PubMed  Google Scholar 

  45. M.R. Eftink, and C.A. Ghiron. Exposure of tryptophanyl residues in proteins. Quantitative determination by fluorescence quenching studies. Biochemistry 15: 672–680 (1976).

    Article  CAS  PubMed  Google Scholar 

  46. J.R. Lakowicz. Principles of Fluorescence Spectroscopy. Plenum Press, New York (1983).

    Book  Google Scholar 

  47. E.A. Burstein, N.S. Vedenkina, and M.N. Ivkova. Fluorescence and the location of tryptophan residues in protein molecules. Photochem. Photobiol. 18:263–279 (1973).

    Article  CAS  PubMed  Google Scholar 

  48. O.K. Gasymov, A.R. Abduragimov, N. Yusifov, and B.J. Glasgow. Solution structure by site directed tryptophan fluorescence in tear lipocalin. Biochem. Biophys. Res. Commun. 239:191–196 (1997).

    Article  CAS  PubMed  Google Scholar 

  49. B.J. Glasgow, O.K. Gasymov, A.R. Abduragimov, T.N. Yusifov, C. Altenbach, and W.L. Hubbell. Side chain mobility and ligand interactions of the G strand of tear lipocalins by site-directed spin labeling. Biochemistry 38:13707–13716 (1999).

    Article  CAS  PubMed  Google Scholar 

  50. W.L. Hubbell, A. Gross, R. Langen, and M.A. Leitzow. Recent advances in site-directed spin labeling of proteins. Curr. Opin. Struct. Biol. 8:649–656 (1998).

    Article  CAS  PubMed  Google Scholar 

  51. O.K. Gasymov, A.R. Abduragimov, T.N. Yusifov, and B.J. Glasgow. Resolution of ligand positions by site directed tryptophan fluorescence in tear lipocalin. Protein Science 9:325–331 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Ophthalmology, Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, Calfornia, USA

    Ben J. Glasgow & Adil R. Abduragimov

  2. Department of Pathology, Jules Stein Eye Institute, UCLA School of Medicine, Los Angeles, Calfornia, USA

    Ben J. Glasgow, Oktay K. Gasymov & Taleh N. Yusifov

Authors
  1. Ben J. Glasgow
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Adil R. Abduragimov
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Oktay K. Gasymov
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Taleh N. Yusifov
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Schepens Eye Research Institute, Boston, Massachusetts, USA

    David A. Sullivan , Darlene A. Dartt  & Rose M. Sullivan ,  & 

  2. Harvard Medical School, Boston, Massachusetts, USA

    David A. Sullivan  & Darlene A. Dartt  & 

  3. Allergan, Inc., Irvine, California, USA

    Michael E. Stern

  4. Tokyo Dental College, Chiba, Japan

    Kazuo Tsubota

  5. Ichikawa General Hospital, Chiba, Japan

    Kazuo Tsubota

  6. University of New Orleans, New Orleans, Louisiana, USA

    B. Britt Bromberg

Rights and permissions

Reprints and permissions

Copyright information

© 2002 Kluwer Academic/Plenum Publishers

About this chapter

Cite this chapter

Glasgow, B.J., Abduragimov, A.R., Gasymov, O.K., Yusifov, T.N. (2002). Tear Lipocalin: Structure, Function and Molecular Mechanisms of Action. In: Sullivan, D.A., Stern, M.E., Tsubota, K., Dartt, D.A., Sullivan, R.M., Bromberg, B.B. (eds) Lacrimal Gland, Tear Film, and Dry Eye Syndromes 3. Advances in Experimental Medicine and Biology, vol 506. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-0717-8_78

Download citation

  • DOI: https://doi.org/10.1007/978-1-4615-0717-8_78

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4613-5208-2

  • Online ISBN: 978-1-4615-0717-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation