[cite journal | author = Sanghi S, Kumar R, Lumsden A, Dickinson D, Klepeis V, Trinkaus-Randall V, Frierson HF Jr, Laurie GW | title = cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland | journal = Journal of molecular biology | volume = 310 | issue = 1 | pages = 127–39 | year = 2001 | month = June | pmid = 11419941 | doi = 10.1006/jmbi.2001.4748 | url = ] Infobox neurotransmitter]
name = Lacritin
abbrev = LACRT
sources = lacrimal, meibomian and salivary glands; corneal and conjunctival epithelia
targets = epithelial specificity
receptors = syndecan-1 (SDC1 but not SDC2 or SDC4) as coreceptor; requires active heparanase (HPSE) to expose a protein core binding site; Signaling receptor: a GPCR is suspected (lacritin mitogenic signaling is pertussis toxin inhibitable); Site of Binding: between N-terminus of SDC1 and C-terminus of lacritin
footnotes = preclinical studies suggest utility in increasing ocular tearingFunction
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.
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.
tructure
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.
pecies distribution
Genomic sequencing assembled by Ensembl reveals the existence of putative lacritin orthologues in other species including:[cite web | url = http://www.ensembl.org/Homo_sapiens/geneview?gene=ENSG00000135413 | title = Gene report for ENSG00000135413 | author = | authorlink = | coauthors = | date = | format = | work = Ensembl release 50: Homo sapiens | publisher = | pages = | language = | archiveurl = | archivedate = | quote = | accessdate = ] "Dasypus novemcinctus" (nine-banded armadillo), "Echinops telfairi" (lesser hedgehog), "Felis silvestris 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).]References
Further reading
*cite journal | author = McKown RL, Wang N, Raab RW, Karnati R, Zhang Y, Williams PB, Laurie GW | title = Lacritin and other new proteins of the lacrimal functional unit | journal = Experimental eye research | volume = | issue = | pages = | year = 2008 | month = September | pmid = 18840430 | doi = 10.1016/j.exer.2008.09.002 | url =
*cite journal | author = Laurie GW, Olsakovsky LA, Conway BP, McKown RL, Kitagawa K, Nichols JJ| title = Dry eye and designer ophthalmics | journal = Optometry and vision science : official publication of the American Academy of Optometry | volume = 85 | issue = 8 | pages = 643–52 | year = 2008 | month = August | pmid = 18677231 | doi = 10.1097/OPX.0b013e318181ae73 | url =
*cite journal | author = Green-Church KB, Nichols JJ | title = Mass spectrometry-based proteomic analyses of contact lens deposition | journal = Molecular vision | volume = 14 | issue = | pages = 291–7 | year = 2008 | pmid = 18334948 | pmc = 2254969 | doi = | url = http://www.molvis.org/molvis/v14/a36/ | issn =
*cite journal | author = Nakajima T, Walkup RD, Tochigi A, Shearer TR, Azuma M | title = Establishment of an appropriate animal model for lacritin studies: cloning and characterization of lacritin in monkey eyes | journal = Experimental eye research | volume = 85 | issue = 5 | pages = 651–8 | year = 2007 | month = November | pmid = 17850790 | doi = 10.1016/j.exer.2007.07.019 | url =
*cite journal | author = Ma P, Beck SL, Raab RW, McKown RL, Coffman GL, Utani A, Chirico WJ, Rapraeger AC, Laurie GW | title = Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin | journal = The Journal of cell biology | volume = 174 | issue = 7 | pages = 1097–106 | year = 2006 | month = September | pmid = 16982797 | pmc = 1666580 | doi = 10.1083/jcb.200511134 | url =
*cite journal | author = Wang J, Wang N, Xie J, Walton SC, McKown RL, Raab RW, Ma P, Beck SL, Coffman GL, Hussaini IM, Laurie GW | title = Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways | journal = The Journal of cell biology | volume = 174 | issue = 5 | pages = 689–700 | year = 2006 | month = August | pmid = 16923831 | pmc = 1761701 | doi = 10.1083/jcb.200605140 | url =
*cite journal | author = Tsai PS, Evans JE, Green KM, Sullivan RM, Schaumberg DA, Richards SM, Dana MR, Sullivan DA | title = Proteomic analysis of human meibomian gland secretions | journal = The British journal of ophthalmology | volume = 90 | issue = 3 | pages = 372–7 | year = 2006 | month = March | pmid = 16488965 | doi = 10.1136/bjo.2005.080846 | url =
*cite journal | author = Zhou L, Beuerman RW, Foo Y, Liu S, Ang LP, Tan DT | title = Characterisation of human tear proteins using high-resolution mass spectrometry | journal = Annals of the Academy of Medicine, Singapore | volume = 35 | issue = 6 | pages = 400–7 | year = 2006 | month = June | pmid = 16865190 | doi = | url = http://www.annals.edu.sg/pdf/35VolNo6200607/V35N6p400.pdf | issn =
*cite journal | author = Koo BS, Lee DY, Ha HS, Kim JC, Kim CW | title = Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis | journal = Journal of proteome research | volume = 4 | issue = 3 | pages = 719–24 | year = 2005 | pmid = 15952718 | doi = 10.1021/pr0498133 | url =
*cite journal | author = Ozyildirim AM, Wistow GJ, Gao J, Wang J, Dickinson DP, Frierson HF Jr, Laurie GW | title = The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts | journal = Investigative ophthalmology & visual science | volume = 46 | issue = 5 | pages = 1572–80 | year = 2005 | month = May | pmid = 15851553 | doi = 10.1167/iovs.04-1380 | url =
*cite journal | author = Kumar R, Huebner A, Laurie GW | title = Genetic separation of the human lacritin gene ("LACRT") and triple A (Allgrove) syndrome on 12q13 | journal = Advances in experimental medicine and biology | volume = 506 | issue = Pt A | pages = 167–74 | year = 2002 | pmid = 12613904 | doi = | url = | issn = PBB_Further_reading
citations =
*cite journal | author=Sanghi S, Kumar R, Lumsden A, "et al." |title=cDNA and genomic cloning of lacritin, a novel secretion enhancing factor from the human lacrimal gland. |journal=J. Mol. Biol.|volume=310 |issue= 1 |pages= 127–39 |year= 2001 |pmid= 11419941 |doi= 10.1006/jmbi.2001.4748
*cite journal | author=Strausberg RL, Feingold EA, Grouse LH, "et al." |title=Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=99 |issue= 26 |pages= 16899–903 |year= 2003 |pmid= 12477932 |doi= 10.1073/pnas.242603899
*cite journal | author=Kumar R, Huebner A, Laurie GW |title=Genetic separation of the human lacritin gene ("LACRT") and triple A (Allgrove) syndrome on 12q13. |journal=Adv. Exp. Med. Biol. |volume=506|issue= Pt A |pages= 167–74 |year= 2003 |pmid= 12613904 |doi=
*cite journal | author=Weigelt B, Bosma AJ, van 't Veer LJ |title=Expression of a novel lacrimal gland gene lacritin in human breast tissues. |journal=J. Cancer Res. Clin. Oncol. |volume=129 |issue= 12 |pages= 735–6 |year= 2004 |pmid= 14574570 |doi= 10.1007/s00432-003-0514-y
*cite journal | author=Gerhard DS, Wagner L, Feingold EA, "et al." |title=The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). |journal=Genome Res.|volume=14 |issue= 10B |pages= 2121–7 |year= 2004 |pmid= 15489334 |doi= 10.1101/gr.2596504
*cite journal | author=Ozyildirim AM, Wistow GJ, Gao J, "et al." |title=The lacrimal gland transcriptome is an unusually rich source of rare and poorly characterized gene transcripts.|journal=Invest. Ophthalmol. Vis. Sci. |volume=46 |issue= 5 |pages= 1572–80 |year= 2005 |pmid= 15851553|doi= 10.1167/iovs.04-1380
*cite journal | author=Koo BS, Lee DY, Ha HS, "et al." |title=Comparative analysis of the tear protein expression in blepharitis patients using two-dimensional electrophoresis. |journal=J. Proteome Res. |volume=4 |issue= 3 |pages= 719–24 |year= 2005 |pmid= 15952718 |doi= 10.1021/pr0498133
*cite journal | author=Tsai PS, Evans JE, Green KM, "et al." |title=Proteomic analysis of human meibomian gland secretions. |journal=The British journal of ophthalmology |volume=90 |issue= 3 |pages= 372–7 |year= 2006 |pmid= 16488965 |doi= 10.1136/bjo.2005.080846
*cite journal | author=Ramachandran P, Boontheung P, Xie Y, "et al." |title=Identification of N-linked glycoproteins in human saliva by glycoprotein capture and mass spectrometry. |journal=J. Proteome Res. |volume=5 |issue= 6 |pages= 1493–503 |year= 2006 |pmid= 16740002 |doi= 10.1021/pr050492k
*cite journal | author=Zhou L, Beuerman RW, Foo Y, "et al." |title=Characterisation of human tear proteins using high-resolution mass spectrometry. |journal=Ann. Acad. Med. Singap. |volume=35 |issue= 6|pages= 400–7 |year= 2007 |pmid= 16865190 |doi=
*cite journal | author=Wang J, Wang N, Xie J, "et al." |title=Restricted epithelial proliferation by lacritin via PKCalpha-dependent NFAT and mTOR pathways. |journal=J. Cell Biol. |volume=174 |issue= 5|pages= 689–700 |year= 2006 |pmid= 16923831 |doi= 10.1083/jcb.200605140
*cite journal | author=Ma P, Beck SL, Raab RW, "et al." |title=Heparanase deglycanation of syndecan-1 is required for binding of the epithelial-restricted prosecretory mitogen lacritin. |journal=J. Cell Biol.|volume=174 |issue= 7 |pages= 1097–106 |year= 2006 |pmid= 16982797 |doi= 10.1083/jcb.200511134
External links
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require_manual_inspection = no
update_protein_box = yes
update_summary = no
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