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:
^
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