LAMP2

Lysosomal-associated membrane protein 2
Available structures
PDB Ortholog search: PDBe, RCSB
Identifiers
Symbols LAMP2 ; CD107b; LAMP-2; LAMPB; LGP110
External IDs OMIM: 309060 MGI: 96748 HomoloGene: 7809 GeneCards: LAMP2 Gene
RNA expression pattern
More reference expression data
Orthologs
Species Human Mouse
Entrez 3920 16784
Ensembl ENSG00000005893 ENSMUSG00000016534
UniProt P13473 P17047
RefSeq (mRNA) NM_001122606 NM_001017959
RefSeq (protein) NP_001116078 NP_001017959
Location (UCSC) Chr X:
120.43 – 120.47 Mb		 Chr X:
38.4 – 38.46 Mb
PubMed search

Lysosome-associated membrane protein 2 (LAMP2) also known as CD107b (Cluster of Differentiation 107b), is a human gene.

The protein encoded by this gene is a member of a family of membrane glycoproteins. This glycoprotein provides selectins with carbohydrate ligands. It may play a role in tumor cell metastasis. It may also function in the protection, maintenance, and adhesion of the lysosome. Alternative splicing of the gene produces three variants - LAMP-2A, LAMP-2B and LAMP-2C.[1] LAMP-2A is the receptor for chaperone-mediated autophagy. Recently it has been determined that antibodies against LAMP-2 account for a fraction of patients who get a serious kidney disease termed focal necrotizing glomerulonephritis.

LAMP-2B is associated with Danon disease.

Genetic Structure

The gene for LAMP2 has 9 coding exons and 2 alternate last exons, 9a and 9b.[2] When the last exon is spliced with the alternative exon, it is a variant called LAMP2b, which varies in the last 11 amino acids of its C-terminal sequence: in the luminal domain, the transmembrane domain, and the cytoplasmic tail. The original (LAMP2a) is highly expressed in the placenta, lung, and liver, while LAMP2b is highly expressed in skeletal muscle.[3]

Biological Function

Lysosomes are cell organelles found in most animal cells. Their main functions center around breaking down materials and debris in the cell. Some of this is done via acid hydrolases that degrade foreign materials and have specialized autolytic functions. These hydrolyses are stored in the lysosomal membrane, which also house lysosomal membrane glycoproteins.[2]

LAMP1 and LAMP2 make up about 50% of lysosomal membrane glycoproteins. (See LAMP1 for more information on both LAMP1 and LAMP2.) Both of these consist of polypeptides of about 40 kD, with the core polypeptide surrounded by 16 to 20 attached N-linked saccharides.[2] The biological functions of these glycoproteins are disputed.[4] They are believed to be significantly involved in operations of the lysosomes, including maintaining integrity, pH and catabolism. Further, some of the functions of LAMP2 are believed to be protecting the lysosomal membrane from proteolytic enzymes that are within the lysosome itself (as in autodigestion), acting as a receptor into the lysosome for proteins, adhesion (when expressed on the outside surface of the plasma membrane) and signal transduction, both inter- and intra-. It also provides protection for the cell from methylating mutagens.[2]

Role in Cancer

LAMP2 has been specifically implicated in tumor cell metastasis.[5] Both LAMP1 and LAMP2 have been found expressed on the surface of cancerous tumors, specifically in cells of highly metastatic cancer such as colon cancer and melanoma.[4] They are rarely found on the plasma membranes of normal cells, and are found more on highly metastatic tumors than on poorly metastatic ones. LAMP2, along with LAMP1, interact with E-selectin and galectins to mediate the adhesion of some cancer cells to the ECM. The two LAMP molecules act as ligands for the cell-adhesion molecules.[6]

It has also been shown that the down-regulation of LAMP2 could both reduce the resistance of breast cancer cells to the paclitaxel[7] and could inhibit cell proliferation in multiple myeloma cells.[8]

Along with other genes such as LC3B, p62 and CTSB, a strong up regulation of LAMP2 was detected in perinecrotic areas of glioblastomas. This suggests autophagy induction in gliomas could be caused by micro-environmental changes.[9]

In a study of glial tumors, the cell membranes of glial and endothelial cells were found to contain LAMP1 and LAMP2, while YKL-40 (a different glycoprotein) was found in the cytoplasm. This suggests that the three glycoproteins are involved in tumor development, specifically in the processes of angiogenesis and tissue remodeling.[10]

See also

References

  1. ↑ "Entrez Gene: LAMP2 lysosomal-associated membrane protein 2".
  2. 1 2 3 4 "OMIM Entry - * 309060 - LYSOSOME-ASSOCIATED MEMBRANE PROTEIN 2; LAMP2". www.omim.org. Retrieved 2016-04-18.
  3. ↑ Konecki, D. S.; Foetisch, K.; Zimmer, K. P.; Schlotter, M.; Lichter-Konecki, U. (1995-10-13). "An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner". Biochemical and Biophysical Research Communications 215 (2): 757–767. ISSN 0006-291X. PMID 7488019.
  4. 1 2 Sarafian, V.; Jadot, M.; Foidart, J. M.; Letesson, J. J.; Van den Brûle, F.; Castronovo, V.; Wattiaux, R.; Coninck, S. W. (1998-01-05). "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. ISSN 0020-7136. PMID 9426697.
  5. ↑ "LAMP2 - Lysosome-associated membrane glycoprotein 2 precursor - Homo sapiens (Human) - LAMP2 gene & protein". www.uniprot.org. Retrieved 2016-04-18.
  6. ↑ "LAMP1". Wikipedia, the free encyclopedia.
  7. ↑ Han, Qi; Chen, Sha; Yang, Mingzhen; Zhang, Zhujun; Chen, An; Hu, Chuanmin; Li, Shuhui (2014-04-01). "[The effect of LAMP2A shRNA on the resistance of breast cancer cells to paclitaxel]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology 30 (4): 351–354. ISSN 1007-8738. PMID 24721399.
  8. ↑ Li, Lixuan; Li, Jia (2015-05-01). "[Lentivirus-mediated shRNA silencing of LAMP2A inhibits the proliferation of multiple myeloma cells]". Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi = Chinese Journal of Cellular and Molecular Immunology 31 (5): 605–608, 614. ISSN 1007-8738. PMID 25940285.
  9. ↑ Jennewein, Lukas; Ronellenfitsch, Michael W.; Antonietti, Patrick; Ilina, Elena I.; Jung, Jennifer; Stadel, Daniela; Flohr, Lisa-Marie; Zinke, Jenny; von Renesse, Janusz (2016-03-04). "Diagnostic and clinical relevance of the autophago-lysosomal network in human gliomas". Oncotarget. doi:10.18632/oncotarget.7910. ISSN 1949-2553. PMID 26956048.
  10. ↑ Kazakova, Maria Hr; Staykov, Dmitrii G.; Koev, Ilian G.; Kitov, Borislav D.; Sarafian, Victoria S. (2014-09-01). "A comparative study of LAMPs and YKL-40 tissue expression in glial tumors". Folia Medica 56 (3): 194–198. ISSN 0204-8043. PMID 25507675.

Further reading

  • Chang MH, Karageorgos LE, Meikle PJ (2003). "CD107a (LAMP-1) and CD107b (LAMP-2).". J. Biol. Regul. Homeost. Agents 16 (2): 147–51. PMID 12144129. 
  • Schleutker J, Haataja L, Renlund M, et al. (1992). "Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease.". Hum. Genet. 88 (1): 95–7. doi:10.1007/BF00204936. PMID 1959930. 
  • Manoni M, Tribioli C, Lazzari B, et al. (1991). "The nucleotide sequence of a CpG island demonstrates the presence of the first exon of the gene encoding the human lysosomal membrane protein lamp2 and assigns the gene to Xq24.". Genomics 9 (3): 551–4. doi:10.1016/0888-7543(91)90424-D. PMID 2032724. 
  • Carlsson SR, Fukuda M (1990). "The polylactosaminoglycans of human lysosomal membrane glycoproteins lamp-1 and lamp-2. Localization on the peptide backbones.". J. Biol. Chem. 265 (33): 20488–95. PMID 2243102. 
  • Mattei MG, Matterson J, Chen JW, et al. (1990). "Two human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2, are encoded by genes localized to chromosome 13q34 and chromosome Xq24-25, respectively.". J. Biol. Chem. 265 (13): 7548–51. PMID 2332441. 
  • Mane SM, Marzella L, Bainton DF, et al. (1989). "Purification and characterization of human lysosomal membrane glycoproteins.". Arch. Biochem. Biophys. 268 (1): 360–78. doi:10.1016/0003-9861(89)90597-3. PMID 2912382. 
  • Fukuda M, Viitala J, Matteson J, Carlsson SR (1989). "Cloning of cDNAs encoding human lysosomal membrane glycoproteins, h-lamp-1 and h-lamp-2. Comparison of their deduced amino acid sequences.". J. Biol. Chem. 263 (35): 18920–8. PMID 3198605. 
  • Dahlgren C, Carlsson SR, Karlsson A, et al. (1995). "The lysosomal membrane glycoproteins Lamp-1 and Lamp-2 are present in mobilizable organelles, but are absent from the azurophil granules of human neutrophils.". Biochem. J. 311 (2): 667–74. PMC: 1136051. PMID 7487911. 
  • Konecki DS, Foetisch K, Zimmer KP, et al. (1995). "An alternatively spliced form of the human lysosome-associated membrane protein-2 gene is expressed in a tissue-specific manner.". Biochem. Biophys. Res. Commun. 215 (2): 757–67. doi:10.1006/bbrc.1995.2528. PMID 7488019. 
  • Konecki DS, Foetisch K, Schlotter M, Lichter-Konecki U (1995). "Complete cDNA sequence of human lysosome-associated membrane protein-2.". Biochem. Biophys. Res. Commun. 205 (1): 1–5. doi:10.1006/bbrc.1994.2620. PMID 7999007. 
  • Carlsson SR, Lycksell PO, Fukuda M (1993). "Assignment of O-glycan attachment sites to the hinge-like regions of human lysosomal membrane glycoproteins lamp-1 and lamp-2.". Arch. Biochem. Biophys. 304 (1): 65–73. doi:10.1006/abbi.1993.1322. PMID 8323299. 
  • Sawada R, Jardine KA, Fukuda M (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.". J. Biol. Chem. 268 (12): 9014–22. PMID 8517882. 
  • Kannan K, Stewart RM, Bounds W, et al. (1996). "Lysosome-associated membrane proteins h-LAMP1 (CD107a) and h-LAMP2 (CD107b) are activation-dependent cell surface glycoproteins in human peripheral blood mononuclear cells which mediate cell adhesion to vascular endothelium.". Cell. Immunol. 171 (1): 10–9. doi:10.1006/cimm.1996.0167. PMID 8660832. 
  • Israels SJ, McMillan EM, Robertson C, et al. (1996). "The lysosomal granule membrane protein, LAMP-2, is also present in platelet dense granule membranes.". Thromb. Haemost. 75 (4): 623–9. PMID 8743190. 
  • Aumüller G, Renneberg H, Hasilik A (1997). "Distribution and subcellular localization of a lysosome-associated protein in human genital organs.". Cell Tissue Res. 287 (2): 335–42. doi:10.1007/s004410050758. PMID 8995204. 
  • Akasaki K, Michihara A, Fujiwara Y, et al. (1997). "Biosynthetic transport of a major lysosome-associated membrane glycoprotein 2, lamp-2: a significant fraction of newly synthesized lamp-2 is delivered to lysosomes by way of early endosomes.". J. Biochem. 120 (6): 1088–94. doi:10.1093/oxfordjournals.jbchem.a021526. PMID 9010755. 
  • Karlsson K, Carlsson SR (1998). "Sorting of lysosomal membrane glycoproteins lamp-1 and lamp-2 into vesicles distinct from mannose 6-phosphate receptor/gamma-adaptin vesicles at the trans-Golgi network.". J. Biol. Chem. 273 (30): 18966–73. doi:10.1074/jbc.273.30.18966. PMID 9668075. 
  • Ayala P, Lin L, Hopper S, et al. (1998). "Infection of epithelial cells by pathogenic neisseriae reduces the levels of multiple lysosomal constituents.". Infect. Immun. 66 (10): 5001–7. PMC: 108621. PMID 9746610. 
  • Furuta K, Yang XL, Chen JS, et al. (1999). "Differential expression of the lysosome-associated membrane proteins in normal human tissues.". Arch. Biochem. Biophys. 365 (1): 75–82. doi:10.1006/abbi.1999.1147. PMID 10222041. 
  • Nishino I, Fu J, Tanji K, et al. (2000). "Primary LAMP-2 deficiency causes X-linked vacuolar cardiomyopathy and myopathy (Danon disease).". Nature 406 (6798): 906–10. doi:10.1038/35022604. PMID 10972294. 

External links

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