Lysosomal-associated membrane protein 1 (LAMP-1) also known as lysosome-associated membrane glycoprotein 1 and CD107a (Cluster of Differentiation 107a), is a protein that in humans is encoded by the LAMP1gene. The human LAMP1 gene is located on the long arm (q) of chromosome 13 at region 3, band 4 (13q34).
Residing primarily across lysosomal membranes, these glycoproteins consist of a large, highly glycosylated end with N-linked carbon chains on the luminal side of the membrane, and a short C-terminal tail[2] exposed to the cytoplasm.[4] The extracytoplasmic region contains a hinge-like structure which can form disulphide bridges homologous to those observed in human immunoglobulin A.[4] Other characteristics of the structure of the LAMP-1 glycoproteins include:
poly-N-acetyllactosamine groups which are involved in interactions with selectin and other glycan-binding proteins[7]
Function
LAMP1 and LAMP2 glycoproteins comprise 50% of all lysosomal membrane proteins,[2] and are thought to be responsible in part for maintaining lysosomal integrity, pH and catabolism.[2][7] The expression of LAMP1 and LAMP2 glycoproteins are linked, as deficiencies in LAMP1 gene will lead to increased expression of LAMP2 glycoproteins.[7] The two are therefore thought to share similar functions in vivo.[2] However, this makes the determining the precise function of LAMP1 difficult, because while the LAMP1 deficient phenotype is little different than the wild type due to LAMP2 up regulation,[2][7] the LAMP1/LAMP2 double deficient phenotype leads to embryonic lethality.[7]
Although the LAMP1 glycoproteins primarily reside across lysosomal membranes, in certain cases they can be expressed across the plasma membrane of the cell.[7] Expression of LAMP1 at the cell surface can occur due to lysosomal fusion with the cell membrane.[8] Cell surface expression of LAMP1 can serve as a ligand for selectins[9][10] and help mediate cell-cell adhesion.[11] Accordingly, cell surface expression of LAMP1 is seen in cells with migratory or invasive functions, such as cytotoxic T cells, platelets and macrophages.[12] Cell surface expression of LAMP1 and LAMP2 is also often seen in cancer cells,[12][13] particularly cancers with high metastatic potential, such as colon carcinoma and melanoma,[12] and has been shown to correlate with their metastatic potential.[7]
Role in cancer
LAMP1 expression on the surface of tumor cells has been observed for a number of different cancer types, particularly in highly metastatic cancers such as pancreatic cancer,[14][15]colon cancer[12][13] and melanoma.[12][13] The structure of LAMP1 correlates with differentiation[4][16] and metastatic potential[7] of tumor cells as it is thought to help mediate cell-cell adhesion [13] and migration.[11][14] Indeed, the adhesion of some cancer cells to the extracellular matrix is mediated by interactions between LAMP1 and LAMP2 and E-selectin and galectins, with the LAMPs serving as ligands for the cell-adhesion molecules.[13]
Cell membrane expression of LAMP-1 observed in the following cancer types:
↑ 4.04.14.24.34.4Carlsson SR, Fukuda M (Dec 1989). "Structure of human lysosomal membrane glycoprotein 1. Assignment of disulfide bonds and visualization of its domain arrangement". The Journal of Biological Chemistry. 264 (34): 20526–31. PMID2584229.
↑ 6.06.16.2Carlsson SR, Roth J, Piller F, Fukuda M (Dec 1988). "Isolation and characterization of human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Major sialoglycoproteins carrying polylactosaminoglycan". The Journal of Biological Chemistry. 263 (35): 18911–9. PMID3143719.
↑ 7.07.17.27.37.47.57.67.7Andrejewski N, Punnonen EL, Guhde G, Tanaka Y, Lüllmann-Rauch R, Hartmann D, von Figura K, Saftig P (Apr 1999). "Normal lysosomal morphology and function in LAMP-1-deficient mice". The Journal of Biological Chemistry. 274 (18): 12692–701. doi:10.1074/jbc.274.18.12692. PMID10212251.
↑Kima, P. E.; Burleigh, B.; Andrews, N. W. (Dec 2000). "Surface-targeted lysosomal membrane glycoprotein-1 (Lamp-1) enhances lysosome exocytosis and cell invasion by Trypanosoma cruzi". Cellular Microbiology. 2 (6): 477–486. doi:10.1046/j.1462-5822.2000.00071.x. ISSN1462-5814. PMID11207602.
↑Sawada R, Jardine KA, Fukuda M (Apr 1993). "The genes of major lysosomal membrane glycoproteins, lamp-1 and lamp-2. 5'-flanking sequence of lamp-2 gene and comparison of exon organization in two genes". The Journal of Biological Chemistry. 268 (12): 9014–9022. PMID8517882.
↑ 11.011.1Acevedo-Schermerhorn C, Gray-Bablin J, Gama R, McCormick PJ (Nov 1997). "t-complex-associated embryonic surface antigen homologous to mLAMP-1. II. Expression and distribution analyses". Experimental Cell Research. 236 (2): 510–518. doi:10.1006/excr.1997.3752. PMID9367636.
↑ 15.015.1Künzli BM, Berberat PO, Zhu ZW, Martignoni M, Kleeff J, Tempia-Caliera AA, Fukuda M, Zimmermann A, Friess H, Büchler MW (Jan 2002). "Influences of the lysosomal associated membrane proteins (Lamp-1, Lamp-2) and Mac-2 binding protein (Mac-2-BP) on the prognosis of pancreatic carcinoma". Cancer. 94 (1): 228–239. doi:10.1002/cncr.10162. PMID11815981.
↑Lee N, Wang WC, Fukuda M (Nov 1990). "Granulocytic differentiation of HL-60 cells is associated with increase of poly-N-acetyllactosamine in Asn-linked oligosaccharides attached to human lysosomal membrane glycoproteins". The Journal of Biological Chemistry. 265 (33): 20476–87. PMID2243101.
Further reading
Chang MH, Karageorgos LE, Meikle PJ (2003). "CD107a (LAMP-1) and CD107b (LAMP-2)". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 147–51. PMID12144129.
Schleutker J, Haataja L, Renlund M, Puhakka L, Viitala J, Peltonen L, Aula P (Nov 1991). "Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease". Human Genetics. 88 (1): 95–7. doi:10.1007/BF00204936. PMID1959930.
Carlsson SR, Fukuda M (Nov 1990). "The polylactosaminoglycans of human lysosomal membrane glycoproteins lamp-1 and lamp-2. Localization on the peptide backbones". The Journal of Biological Chemistry. 265 (33): 20488–95. PMID2243102.
Mattei MG, Matterson J, Chen JW, Williams MA, Fukuda M (May 1990). "Two human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2, are encoded by genes localized to chromosome 13q34 and chromosome Xq24-25, respectively". The Journal of Biological Chemistry. 265 (13): 7548–51. PMID2332441.
Carlsson SR, Fukuda M (Dec 1989). "Structure of human lysosomal membrane glycoprotein 1. Assignment of disulfide bonds and visualization of its domain arrangement". The Journal of Biological Chemistry. 264 (34): 20526–31. PMID2584229.
Mane SM, Marzella L, Bainton DF, Holt VK, Cha Y, Hildreth JE, August JT (Jan 1989). "Purification and characterization of human lysosomal membrane glycoproteins". Archives of Biochemistry and Biophysics. 268 (1): 360–78. doi:10.1016/0003-9861(89)90597-3. PMID2912382.
Fukuda M, Viitala J, Matteson J, Carlsson SR (Dec 1988). "Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences". The Journal of Biological Chemistry. 263 (35): 18920–8. PMID3198605.
Ohno H, Stewart J, Fournier MC, Bosshart H, Rhee I, Miyatake S, Saito T, Gallusser A, Kirchhausen T, Bonifacino JS (Sep 1995). "Interaction of tyrosine-based sorting signals with clathrin-associated proteins". Science. 269 (5232): 1872–5. doi:10.1126/science.7569928. PMID7569928.
Carlsson SR, Lycksell PO, Fukuda M (Jul 1993). "Assignment of O-glycan attachment sites to the hinge-like regions of human lysosomal membrane glycoproteins lamp-1 and lamp-2". Archives of Biochemistry and Biophysics. 304 (1): 65–73. doi:10.1006/abbi.1993.1322. PMID8323299.
Sawada R, Jardine KA, Fukuda M (Apr 1993). "The genes of major lysosomal membrane glycoproteins, lamp-1 and lamp-2. 5'-flanking sequence of lamp-2 gene and comparison of exon organization in two genes". The Journal of Biological Chemistry. 268 (12): 9014–22. PMID8517882.
Furuta K, Yang XL, Chen JS, Hamilton SR, August JT (May 1999). "Differential expression of the lysosome-associated membrane proteins in normal human tissues". Archives of Biochemistry and Biophysics. 365 (1): 75–82. doi:10.1006/abbi.1999.1147. PMID10222041.
Raposo G, Moore M, Innes D, Leijendekker R, Leigh-Brown A, Benaroch P, Geuze H (Oct 2002). "Human macrophages accumulate HIV-1 particles in MHC II compartments". Traffic. 3 (10): 718–29. doi:10.1034/j.1600-0854.2002.31004.x. PMID12230470.
Zhang H, Li XJ, Martin DB, Aebersold R (Jun 2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". Nature Biotechnology. 21 (6): 660–6. doi:10.1038/nbt827. PMID12754519.
