Alternative titles; symbols
HGNC Approved Gene Symbol: LAMP1
Cytogenetic location: 13q34 Genomic coordinates (GRCh38): 13:113,297,239-113,323,672 (from NCBI)
The 120-kD lysosomal membrane glycoprotein is an acidic, heavily glycosylated membrane protein enriched in the lysosomal membrane. By using an oligonucleotide probe corresponding to the amino terminus of rat lgp120, Howe et al. (1988) isolated and characterized cDNA clones containing the entire coding region. The deduced amino acid sequence demonstrated that the rat LGP120 contains a putative signal peptide, 18 sites for N-linked glycosylation, a single membrane-spanning segment, and a short (11 amino acid) cytosolic tail. LGP120 showed similarity to 2 other lysosomal membrane proteins and showed a high degree of conservation in domain organization and primary structure with the proteins in other species.
Viitala et al. (1988) reported the complete amino acid sequence for the human lysosome-associated membrane glycoprotein with M(r) about 120,000. The amino acid sequence, which was deduced from analysis of the cDNA, contains 385 amino acid residues.
Mattei et al. (1990) noted that, although LAMP1 contains a functional hinge region, it has a disulfide arrangement different from that observed in members of the immunoglobulin superfamily and thus may represent a novel family of membrane glycoproteins. The amino acid sequence of LAMP1 is more homologous to corresponding molecules from other species than it is to LAMP2 (309060). Furthermore, LAMP1 and LAMP2 are immunologically distinguishable from each other. Mattei et al. (1990) proposed that LAMP1 and LAMP2 diverged relatively early in evolution, but that LAMP1 (and possibly LAMP2) structures have been strongly conserved.
Yogalingam et al. (2008) stated that LAMP1 is involved in lysosomal exocytosis, movement of lysosomes along microtubules, and fusion of phagosomes with lysosomes. They found that hematopoietic cells from neuraminidase-1 (NEU1; 608272) -/- mice, a model of human sialidosis (256550), showed increased plasma membrane expression of a hypersialylated form of Lamp1 compared with wildtype mice. Yogalingam et al. (2008) confirmed that Lamp1, but not other lysosomal membrane proteins, was an endogenous Neu1 substrate. Accumulation of Lamp1 on the plasma membrane of Neu1 -/- macrophages was associated with enhanced exocytosis of lysosomal hydrolases. Overexpression of wildtype Lamp1 did not fully recapitulate the effects of accumulated hypersialylated Lamp1 on lysosomal exocytosis. Reduced Lamp1 expression in both Neu1 -/- and wildtype mouse macrophages via small interfering RNA reduced lysosomal exocytosis, particularly in Neu1 -/- cells. Yogalingam et al. (2008) found that fibroblasts from 2 patients with early-onset (type II) sialidosis due to mutations that eliminated NEU1 activity showed increased plasma membrane LAMP1 compared with normal fibroblasts. In contrast, fibroblasts from a patient with late-onset (type I) sialidosis with residual NEU1 activity exhibited a more normal LAMP1 distribution. The culture medium of type II sialidosis fibroblasts also showed elevated alpha-mannosidase activity (see 609458), suggesting increased lysosomal exocytosis.
Lassa virus, which spreads from rodents to humans, can cause lethal hemorrhagic fever. Despite the broad tropism of the virus, chicken cells were reported 30 years ago to resist infection. Jae et al. (2014) found that Lassa virus readily engaged its cell-surface receptor alpha-dystroglycan (DAG1; 128239) in avian cells, but virus entry in susceptible species involved a pH-dependent switch to an intracellular receptor, LAMP1. Iterative haploid screens revealed that ST3GAL4 (104240) was required for the interaction of the virus glycoprotein with LAMP1. A single glycosylated residue in LAMP1, present in susceptible species but absent in birds, was essential for interaction with the Lassa virus envelope protein and subsequent infection. Lamp1-deficient mice cleared intraperitoneally-injected wildtype Lassa virus by 6 days after injection, whereas infection was manifest in all organ samples taken from wildtype or heterozygous animals.
By means of in situ hybridization, Mattei et al. (1990) assigned the LAMP1 gene to chromosome 13q34. A related gene, which may be a pseudogene, mapped to chromosome 12p13.3. Hybridization of LAMP1 cDNA to chromosome 12p13.3 was observed even when probes representing different portions of the LAMP1 cDNA were used.
Using Southern hybridization in hamster/human hybrid cell panels, Schleutker et al. (1991) confirmed the assignment of the LAMP1 gene to chromosome 13. Furthermore, Schleutker et al. (1991) demonstrated absence of genetic linkage of either LAMP1 or LAMP2 with Salla disease (604369), a condition in which defective function of a lysosomal membrane transporter protein is the probable cause of accumulation of sialic acid in lysosomes.
Bermingham et al. (1996) demonstrated that the Lamp1 gene is located on mouse chromosome 8. They could find no evidence that it is the site of the mutation in mnd (motor neuron degeneration) mice.
Bermingham, N. A., Martin, J. E., Fisher, E. M. C. The mouse lysosomal membrane protein 1 gene as a candidate for the motorneuron degeneration (mnd) locus. Genomics 32: 266-271, 1996. [PubMed: 8833154] [Full Text: https://doi.org/10.1006/geno.1996.0114]
Howe, C. L., Granger, B. L., Hull, M., Green, S. A., Gabel, C. A., Helenius, A., Mellman, I. Derived protein sequence, oligosaccharides, and membrane insertion of the 120-kDa lysosomal membrane glycoprotein (lgp120): identification of a highly conserved family of lysosomal membrane glycoproteins. Proc. Nat. Acad. Sci. 85: 7577-7581, 1988. [PubMed: 3174652] [Full Text: https://doi.org/10.1073/pnas.85.20.7577]
Jae, L. T., Raaben, M., Herbert, A. S., Kuehne, A. I., Wirchnianski, A. S., Soh, T. K., Stubbs, S. H., Janssen, H., Damme, M., Saftig, P., Whelan, S. P., Dye, J. M., Brummelkamp, T. R. Lassa virus entry requires a trigger-induced receptor switch. Science 344: 1506-1510, 2014. [PubMed: 24970085] [Full Text: https://doi.org/10.1126/science.1252480]
Mattei, M.-G., Matterson, J., Chen, J. W., Williams, M. A., Fukuda, M. 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: 7548-7551, 1990. [PubMed: 2332441]
Schleutker, J., Haataja, L., Renlund, M., Puhakka, L., Viitala, J., Peltonen, L., Aula, P. Confirmation of the chromosomal localization of human lamp genes and their exclusion as candidate genes for Salla disease. Hum. Genet. 88: 95-97, 1991. [PubMed: 1959930] [Full Text: https://doi.org/10.1007/BF00204936]
Viitala, J., Carlsson, S. R., Siebert, P. D., Fukuda, M. Molecular cloning of cDNAs encoding lamp A, a human lysosomal membrane glycoprotein with apparent M(r) about 120,000. Proc. Nat. Acad. Sci. 85: 3743-3747, 1988. [PubMed: 3131762] [Full Text: https://doi.org/10.1073/pnas.85.11.3743]
Yogalingam, G., Bonten, E. J., van de Vlekkert, D., Hu, H., Moshiach, S., Connell, S. A., d'Azzo, A. Neuraminidase 1 is a negative regulator of lysosomal exocytosis. Dev. Cell 15: 74-86, 2008. [PubMed: 18606142] [Full Text: https://doi.org/10.1016/j.devcel.2008.05.005]