Lacritin

Lacritin is a common glycoprotein of the human tear film. It is mainly produced by the lacrimal gland. Some lacritin also is produced by the meibomian gland, and also by epithelial cells of the conjunctiva and cornea. The lacritin gene LACRT is one of the most highly transcriptionally regulated genes in the human eye. Functional studies suggest a role in epithelial renewal of some nongermative epithelia. By flowing downstream through ducts, it may generate a 'proliferative field'. Lacritin also promotes secretion. This raises the possibility that lacritin may have clinical applications in the treatment of dry eye, the most common eye disease. Recent studies suggest that lacritin is differentially deregulated in blepharitis.

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One particularly remarkable feature about lacritin is its cell targeting specificity. New studies suggest that the cell surface proteoglycan syndecan-1 is partly responsible. Syndecan-1 binds many growth factors through its heparan sulfate side chains. It also binds lacritin, but interestingly heparan sulfate interferes with lacritin binding. Since syndecan-1's appear to be always decorated with heparan sulfate, this means that heparanase must be available to partially or completely cleave off heparan sulfate allowing lacritin to bind. Thus heparanase regulates lacritin function.

Lacritin consists of 119 amino acids after cleavage of the N-terminal signal peptide. It displays several predicted alpha helices. One near the C-terminus is a predicted amphipathic alpha helix. This alpha helix appears to bind a domain in the N-terminus of syndecan-1.

Genomic sequencing assembled by Ensembl [1] reveals the existence of putative lacritin orthologues in other species [2] including: Dasypus novemcinctus (nine-banded armadillo), Echinops telfairi (lesser hedgehog), Felis catus (house cat), Macaca mulatta (rhesus macaque or monkey), Myotis lucifugus (little brown bat), Pan troglodytes (chimpanzee), Sorex araneus (common shrew) and Tupaia belangeri (northern tree shrew).

Category: Tears

• Ma P, Wang N, McKown RL, Raab RW, Laurie GW (2007). "Focus on Molecules: Lacritin". Exp Eye Res. Feb 16; [Epub ahead of print]. PMID: 17412322. [3]

• Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW (2006). "Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin". J Cell Biol. Sep 25;174(7):1097-106. Epub 2006 Sep 18. PMID: 16982797. [4]

• Wang J, Wang N, Xie J, Walton SC, McKown RL, Raab RW, Ma P, Beck SL, Coffman GL, Hussaini IM, Laurie GW (2006). "Restricted epithelial proliferation by lacritin via PKC{alpha}-dependent NFAT and mTOR pathways". J Cell Biol. 174 (5):689-700. PMID 16923831. [5]

• Tsai PS, Evans JE, Green KM, Sullivan RM, Schaumberg DA, Richards SM, Dana MR, Sullivan DA (2006). "Proteomic analysis of human meibomian gland secretions". Br J Ophthalmol. 90(3):372-377. PMID 16488965. [6]

• Zhou L, Beuerman RW, Foo Y, Liu S, Ang LP, Tan DT (2006). Characterisation of human tear proteins using high-resolution mass spectrometry". Ann Acad Med Singapore. 2006 Jun;35(6):400-7. PMID: 16865190. [7]

• Koo BS, Lee DY, Ha HS, Kim JC, Kim CW (2005). "Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis". J Proteome Res. 4(3):719-724. PMID 15952718. [8]

• Ozyildirim AM, Wistow GJ, Gao J, Wang J, Dickinson DP, Frierson HF Jr, Laurie GW (2005). "The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts". Invest Ophthalmol Vis Sci. 46(5):1572-1580. PMID 15851553. [9]

• Kumar R, Huebner A, Laurie GW (2002). Genetic separation of the human lacritin gene ("LACRT") and triple A (Allgrove) syndrome on 12q13". Adv Exp Med Biol. 2002;506(Pt A):167-74. No abstract available. PMID: 12613904 [PubMed - indexed for MEDLINE]

• Sanghi S, Kumar R, Lumsden A, Dickinson D, Klepeis V, Trinkaus-Randall V, Frierson HF Jr, Laurie GW (2001). "cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland". J Mol Biol. 310 (1):127-139. PMID 11419941.