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[6] exposed to the cytoplasm.[8] The extracytoplasmic region contains a hinge-like structure which can form disulphide bridges homologous to those observed in human immunoglobulin A.[8] 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[11]
Function
LAMP1 and LAMP2 glycoproteins comprise 50% of all lysosomal membrane proteins,[6] and are thought to be responsible in part for maintaining lysosomal integrity, pH and catabolism.[6][11] The expression of LAMP1 and LAMP2 glycoproteins are linked, as deficiencies in LAMP1 gene will lead to increased expression of LAMP2 glycoproteins.[11] The two are therefore thought to share similar functions in vivo.[6] 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,[6][11] the LAMP1/LAMP2 double deficient phenotype leads to embryonic lethality.[11]
Although the LAMP1 glycoproteins primarily reside across lysosomal membranes, in certain cases they can be expressed across the plasma membrane of the cell.[11] Expression of LAMP1 at the cell surface can occur due to lysosomal fusion with the cell membrane.[12] Cell surface expression of LAMP1 can serve as a ligand for selectins[13][14] and help mediate cell-cell adhesion.[15] Accordingly, cell surface expression of LAMP1 is seen in cells with migratory or invasive functions, such as cytotoxic T cells, platelets and macrophages.[16] Cell surface expression of LAMP1 and LAMP2 is also often seen in cancer cells,[16][17] particularly cancers with high metastatic potential, such as colon carcinoma and melanoma,[16] and has been shown to correlate with their metastatic potential.[11]
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,[18][19]colon cancer[16][17] and melanoma.[16][17] The structure of LAMP1 correlates with differentiation[8][20] and metastatic potential[11] of tumor cells as it is thought to help mediate cell-cell adhesion [17] and migration.[15][18] 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.[17]
Cell membrane expression of LAMP-1 observed in the following cancer types:
^ abcdefEskelinen EL (2006). "Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy". Molecular Aspects of Medicine. 27 (5–6): 495–502. doi:10.1016/j.mam.2006.08.005. PMID16973206.
^ abAcevedo-Schermerhorn C, Gray-Bablin J, Gama R, McCormick PJ (November 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.
^ abcdeAgarwal AK, Srinivasan N, Godbole R, More SK, Budnar S, Gude RP, et al. (September 2015). "Role of tumor cell surface lysosome-associated membrane protein-1 (LAMP1) and its associated carbohydrates in lung metastasis". Journal of Cancer Research and Clinical Oncology. 141 (9): 1563–1574. doi:10.1007/s00432-015-1917-2. PMID25614122. S2CID9133450.
^ abKünzli BM, Berberat PO, Zhu ZW, Martignoni M, Kleeff J, Tempia-Caliera AA, et al. (January 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. S2CID12702437.
Chang MH, Karageorgos LE, Meikle PJ (2003). "CD107a (LAMP-1) and CD107b (LAMP-2)". Journal of Biological Regulators and Homeostatic Agents. 16 (2): 147–151. PMID12144129.
Schleutker J, Haataja L, Renlund M, Puhakka L, Viitala J, Peltonen L, et al. (November 1991). "Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease". Human Genetics. 88 (1): 95–97. doi:10.1007/BF00204936. PMID1959930. S2CID31520394.
Mane SM, Marzella L, Bainton DF, Holt VK, Cha Y, Hildreth JE, et al. (January 1989). "Purification and characterization of human lysosomal membrane glycoproteins". Archives of Biochemistry and Biophysics. 268 (1): 360–378. doi:10.1016/0003-9861(89)90597-3. PMID2912382.
Ohno H, Stewart J, Fournier MC, Bosshart H, Rhee I, Miyatake S, et al. (September 1995). "Interaction of tyrosine-based sorting signals with clathrin-associated proteins". Science. 269 (5232): 1872–1875. Bibcode:1995Sci...269.1872O. doi:10.1126/science.7569928. PMID7569928.
Carlsson SR, Lycksell PO, Fukuda M (July 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.
Zhang H, Li XJ, Martin DB, Aebersold R (June 2003). "Identification and quantification of N-linked glycoproteins using hydrazide chemistry, stable isotope labeling and mass spectrometry". Nature Biotechnology. 21 (6): 660–666. doi:10.1038/nbt827. PMID12754519. S2CID581283.
