Biology:LAMP1

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Short description: Protein-coding gene in the species Homo sapiens


A representation of the 3D structure of the protein myoglobin showing turquoise α-helices.
Generic protein structure example

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).

Immunofluorescence staining of HeLa Cells with antibody to reveal lysosomal LAMP1 in red and vimentin containing intermediate filaments in green. Nuclear DNA is seen in blue. Antibodies and image courtesy EnCor Biotechnology Inc.

Lysosomal-associated membrane protein 1 is a glycoprotein 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

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:

  • A polypeptide core of ~40kDa[4]
  • 18 {N-glycosylation} sites to help with the addition of sugar chains[6]
  • Polylactosamine attachments which protect the glyocoprotein from degradation by lysosomal proteases[6]
  • Significant quantities of polylactosaminoglycan and sialic acid to traverse the trans-Golgi cisternae.[6]
  • poly-N-acetyllactosamine groups which are involved in interactions with selectin and other glycan-binding proteins[7]

Function

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

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

References

  1. ↑ 1.0 1.1 "LAMP1 lysosomal-associated membrane protein 1". Entrez Gene. https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=3916. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 "Roles of LAMP-1 and LAMP-2 in lysosome biogenesis and autophagy". Molecular Aspects of Medicine 27 (5–6): 495–502. 2006. doi:10.1016/j.mam.2006.08.005. PMID 16973206. 
  3. ↑ "LAMP1". The Human Protein Atlas. http://www.proteinatlas.org/ENSG00000185896-LAMP1/tissue. 
  4. ↑ 4.0 4.1 4.2 4.3 4.4 "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. Dec 1989. doi:10.1016/S0021-9258(19)47094-4. PMID 2584229. 
  5. ↑ "LAMP1 - lysosomal-associated membrane protein1". Wikigenes. https://www.wikigenes.org/e/gene/e/3916.html. 
  6. ↑ 6.0 6.1 6.2 "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. Dec 1988. doi:10.1016/S0021-9258(18)37369-1. PMID 3143719. 
  7. ↑ 7.0 7.1 7.2 7.3 7.4 7.5 7.6 7.7 "Normal lysosomal morphology and function in LAMP-1-deficient mice". The Journal of Biological Chemistry 274 (18): 12692–701. Apr 1999. doi:10.1074/jbc.274.18.12692. 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. doi:10.1046/j.1462-5822.2000.00071.x. ISSN 1462-5814. PMID 11207602. 
  9. ↑ "Purification of two glycoproteins expressing beta 1-6 branched Asn-linked oligosaccharides from metastatic tumour cells". The Biochemical Journal 259 (2): 569–576. Apr 1989. doi:10.1042/bj2590569. PMID 2719668. 
  10. ↑ "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. Apr 1993. doi:10.1016/S0021-9258(18)52972-0. PMID 8517882. 
  11. ↑ 11.0 11.1 "t-complex-associated embryonic surface antigen homologous to mLAMP-1. II. Expression and distribution analyses". Experimental Cell Research 236 (2): 510–518. Nov 1997. doi:10.1006/excr.1997.3752. PMID 9367636. 
  12. ↑ 12.0 12.1 12.2 12.3 12.4 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 141 (9): 1563–1574. doi:10.1007/s00432-015-1917-2. ISSN 0171-5216. PMID 25614122. 
  13. ↑ 13.0 13.1 13.2 13.3 13.4 13.5 13.6 13.7 "Expression of Lamp-1 and Lamp-2 and their interactions with galectin-3 in human tumor cells". International Journal of Cancer 75 (1): 105–111. Jan 1998. doi:10.1002/(sici)1097-0215(19980105)75:1<105::aid-ijc16>3.0.co;2-f. PMID 9426697. 
  14. ↑ 14.0 14.1 14.2 "Expression of the lysosomal-associated membrane protein-1 (LAMP-1) in astrocytomas". International Journal of Clinical and Experimental Pathology 6 (7): 1294–1305. 2013. PMID 23826410. 
  15. ↑ 15.0 15.1 "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. Jan 2002. doi:10.1002/cncr.10162. PMID 11815981. 
  16. ↑ "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. Nov 1990. doi:10.1016/S0021-9258(17)30529-X. PMID 2243101. 

Further reading

External links


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



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