Lysosomal-associated membrane protein 1 (LAMP-1) also known aslysosome-associated membrane glycoprotein 1 andCD107a (Cluster ofDifferentiation 107a), is aprotein that in humans is encoded by theLAMP1gene. The humanLAMP1 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, highlyglycosylated end with N-linked carbon chains on the luminal side of the membrane, and a short C-terminal tail[6] exposed to thecytoplasm.[8] The extracytoplasmic region contains a hinge-like structure which can formdisulphide bridges homologous to those observed in humanimmunoglobulin A.[8] Other characteristics of the structure of the LAMP-1 glycoproteins include:
LAMP1 andLAMP2 glycoproteins comprise 50% of all lysosomal membrane proteins,[6] and are thought to be responsible in part for maintaining lysosomal integrity, pH andcatabolism.[6][11] The expression of LAMP1 and LAMP2 glycoproteins are linked, as deficiencies inLAMP1 gene will lead to increased expression of LAMP2 glycoproteins.[11] The two are therefore thought to share similar functionsin vivo.[6] However, this makes the determining the precise function of LAMP1 difficult, because while theLAMP1 deficientphenotype is little different than the wild type due toLAMP2 up regulation,[6][11] theLAMP1/LAMP2 double deficient phenotype leads toembryonic 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 lysosomalfusion with the cell membrane.[12] Cell surface expression of LAMP1 can serve as a ligand forselectins[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 ascytotoxic T cells,platelets andmacrophages.[16] Cell surface expression of LAMP1 and LAMP2 is also often seen incancer 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]
LAMP1 expression on the surface of tumor cells has been observed for a number of different cancer types, particularly in highly metastatic cancers such aspancreatic cancer,[18][19]colon cancer[16][17] andmelanoma.[16][17] The structure of LAMP1 correlates withdifferentiation[8][20] and metastatic potential[11] of tumor cells as it is thought to help mediate cell-cell adhesion[17] andmigration.[15][18] Indeed, the adhesion of some cancer cells to theextracellular matrix is mediated by interactions between LAMP1 and LAMP2 andE-selectin andgalectins, with the LAMPs serving as ligands for the cell-adhesion molecules.[17]
Cell membrane expression of LAMP-1 observed in the following cancer types:
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