LAMP1

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Lysosomal-associated membrane protein 1
Identifiers
Symbols LAMP1 ; CD107a; LAMPA; LGP120
External IDs OMIM153330 MGI96745 HomoloGene4061 GeneCards: LAMP1 Gene
RNA expression pattern
PBB GE LAMP1 201553 s at tn.png
PBB GE LAMP1 201551 s at tn.png
PBB GE LAMP1 201552 at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 3916 16783
Ensembl ENSG00000185896 ENSMUSG00000031447
UniProt P11279 P11438
RefSeq (mRNA) NM_005561 NM_010684
RefSeq (protein) NP_005552 NP_034814
Location (UCSC) Chr 13:
113.3 – 113.32 Mb
Chr 8:
13.16 – 13.18 Mb
PubMed search [1] [2]

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 glyoprotein from a family of Lysosome-associated membrane glycoproteins.[1] The LAMP-1 glycoprotein is a type I transmembrane protein[2] which is expressed at high or medium levels in at least 76 different normal tissue cell types.[3] It resides primarily across lysosomal membranes,[4] and functions to provide selectins with carbohydrate ligands.[1] CD107a has also been shown to be a marker of degranulation on lymphocytes such as CD8+ and NK cells.[5] and may also play a role in tumor cell differentiation and metastasis.

Structure[edit]

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:

Function[edit]

LAMP1 and LAMP2 glycoproteins comprise 50% of all lysosomal membrane proteins,[2] and are thought to be responsible in part for maintaining lysosomal integreity, 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[edit]

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:

See also[edit]

References[edit]

  1. ^ a b "LAMP1 lysosomal-associated membrane protein 1". Entrez Gene. 
  2. ^ a b c d e f Eskelinen EL. "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. PMID 16973206. 
  3. ^ "LAMP1". The Human Protein Atlas. 
  4. ^ a b c d e 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. PMID 2584229. 
  5. ^ "LAMP1 - lysosomal-associated membrane protein1". Wikigenes. 
  6. ^ a b c Carlsson 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. PMID 3143719. 
  7. ^ a b c d e f g h Andrejewski 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. PMID 10212251. 
  8. ^ 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. ISSN 1462-5814. PMID 11207602. 
  9. ^ Laferte S, Dennis JW (Apr 1989). "Purification of two glycoproteins expressing beta 1-6 branched Asn-linked oligosaccharides from metastatic tumour cells". The Biochemical Journal 259 (2): 569–576. PMID 2719668. 
  10. ^ 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. PMID 8517882. 
  11. ^ a b Acevedo-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. PMID 9367636. 
  12. ^ a b c d e Agarwal, Akhil Kumar; Srinivasan, Nithya; Godbole, Rashmi; More, Shyam K.; Budnar, Srikanth; Gude, Rajiv P.; Kalraiya, Rajiv D. (2015-01-23). "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: 1–12. doi:10.1007/s00432-015-1917-2. ISSN 0171-5216. 
  13. ^ a b c d e f g h Sarafian V, Jadot M, Foidart JM, Letesson JJ, Van den Brûle F, Castronovo V, Wattiaux R, Coninck SW (Jan 1998). "Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells". International Journal of Cancer. Journal International Du Cancer 75 (1): 105–111. PMID 9426697. 
  14. ^ a b c Jensen SS, Aaberg-Jessen C, Christensen KG, Kristensen B. "Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas". International Journal of Clinical and Experimental Pathology 6 (7): 1294–1305. PMID 23826410. 
  15. ^ a b Künzli 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. PMID 11815981. 
  16. ^ 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. PMID 2243101. 

Further reading[edit]

External links[edit]

This article incorporates text from the United States National Library of Medicine, which is in the public domain.