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 LAMP1 gene. The human LAMP1 gene is located on the long arm (q) of chromosome 13 at region 3, band 4 (13q34).
Lysosomal-associated membrane protein 1 is a glycoprotein from a family of Lysosome-associated membrane glycoproteins. [5] The LAMP-1 glycoprotein is a type I transmembrane protein [6] which is expressed at high or medium levels in at least 76 different normal tissue cell types. [7] It resides primarily across lysosomal membranes, [8] and functions to provide selectins with carbohydrate ligands. [5] CD107a has also been shown to be a marker of degranulation on lymphocytes such as CD8+ and NK cells, [9] and may also play a role in tumor cell differentiation and metastasis.
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:
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]
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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Lysosome-associated membrane glycoproteins (LAMPs) are integral membrane proteins, specific to lysosomes, and whose exact biological function is not yet clear. Structurally, the lamp proteins consist of two internally homologous lysosome-luminal domains separated by a proline-rich hinge region; at the C-terminal extremity there is a transmembrane region (TM) followed by a very short cytoplasmic tail (C). In each of the duplicated domains, there are two conserved disulfide bonds. This structure is schematically represented in the figure below.
+-----+ +-----+ +-----+ +-----+ | | | | | | | | xCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxxxCxxxxxCxxxxxxxxxxxxCxxxxxCxxxxxxxx +--------------------------++Hinge++--------------------------++TM++C+
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This article incorporates text from the United States National Library of Medicine, which is in the public domain.