Laminin subunit gamma-2 explained

Laminin subunit gamma-2 is a protein that in humans is encoded by the LAMC2 gene.^{[1] [2]}

Laminins, a family of extracellular matrix glycoproteins, are the major noncollagenous constituent of basement membranes. They have been implicated in a wide variety of biological processes including cell adhesion, differentiation, migration, signaling, neurite outgrowth and metastasis. Laminins are composed of 3 non identical chains: laminin alpha, beta and gamma (formerly A, B1, and B2, respectively) and they form a cruciform structure consisting of 3 short arms, each formed by a different chain, and a long arm composed of all 3 chains. Each laminin chain is a multidomain protein encoded by a distinct gene.

Several isoforms of each chain have been described. Different alpha, beta and gamma chain isomers combine to give rise to different heterotrimeric laminin isoforms which are designated by Arabic numerals in the order of their discovery, i.e. alpha1beta1gamma1 heterotrimer is laminin 1. The biological functions of the different chains and trimer molecules are largely unknown, but some of the chains have been shown to differ with respect to their tissue distribution, presumably reflecting diverse functions in vivo. This gene encodes the gamma chain isoform laminin, gamma 2. The gamma 2 chain, formerly thought to be a truncated version of beta chain (B2t), is highly homologous to the gamma 1 chain; however, it lacks domain VI, and domains V, IV and III are shorter. It is expressed in several fetal tissues but differently from gamma 1, and is specifically localized to epithelial cells in skin, lung and kidney. The gamma 2 chain together with alpha 3 and beta 3 chains constitute laminin 5 (earlier known as kalinin), which is an integral part of the anchoring filaments that connect epithelial cells to the underlying basement membrane. The epithelium-specific expression of the gamma 2 chain implied its role as an epithelium attachment molecule, and mutations in this gene have been associated with junctional epidermolysis bullosa, a skin disease.

Further reading

• Baudoin C, Miquel C, Gagnoux-Palacios L, etal . A novel homozygous nonsense mutation in the LAMC2 gene in patients with the Herlitz junctional epidermolysis bullosa . Hum. Mol. Genet. . 3 . 10 . 1909–10 . 1995 . 7849725 . 10.1093/hmg/3.10.1909 .
• Burgeson RE, Chiquet M, Deutzmann R, etal . A new nomenclature for the laminins . Matrix Biol. . 14 . 3 . 209–11 . 1994 . 7921537 . 10.1016/0945-053X(94)90184-8 .
• Gedde-Dahl T, Dupuy BM, Jonassen R, etal . Junctional epidermolysis bullosa inversa (locus EBR2A) assigned to 1q31 by linkage and association to LAMC1 . Hum. Mol. Genet. . 3 . 8 . 1387–91 . 1995 . 7987320 . 10.1093/hmg/3.8.1387 .
• Pulkkinen L, Christiano AM, Airenne T, etal . Mutations in the gamma 2 chain gene (LAMC2) of kalinin/laminin 5 in the junctional forms of epidermolysis bullosa . Nat. Genet. . 6 . 3 . 293–7 . 1994 . 8012393 . 10.1038/ng0394-293 . 9915709 .
• Aberdam D, Galliano MF, Vailly J, etal . Herlitz's junctional epidermolysis bullosa is linked to mutations in the gene (LAMC2) for the gamma 2 subunit of nicein/kalinin (LAMININ-5) . Nat. Genet. . 6 . 3 . 299–304 . 1994 . 8012394 . 10.1038/ng0394-299 . 2931644 .
• Miyazaki K, Kikkawa Y, Nakamura A, etal . A large cell-adhesive scatter factor secreted by human gastric carcinoma cells . Proc. Natl. Acad. Sci. U.S.A. . 90 . 24 . 11767–71 . 1994 . 8265624 . 10.1073/pnas.90.24.11767 . 48065 . free .
• Vailly J, Verrando P, Champliaud MF, etal . The 100-kDa chain of nicein/kalinin is a laminin B2 chain variant . Eur. J. Biochem. . 219 . 1–2 . 209–18 . 1994 . 8306988 . 10.1111/j.1432-1033.1994.tb19932.x . free .
• Airenne T, Haakana H, Sainio K, etal . Structure of the human laminin gamma 2 chain gene (LAMC2): alternative splicing with different tissue distribution of two transcripts . Genomics . 32 . 1 . 54–64 . 1996 . 8786121 . 10.1006/geno.1996.0076 .
• Mizushima H, Miyagi Y, Kikkawa Y, etal . Differential expression of laminin-5/ladsin subunits in human tissues and cancer cell lines and their induction by tumor promoter and growth factors . J. Biochem. . 120 . 6 . 1196–202 . 1997 . 9010770 . 10.1093/oxfordjournals.jbchem.a021541.
• Mizushima H, Koshikawa N, Moriyama K, etal . Wide distribution of laminin-5 gamma 2 chain in basement membranes of various human tissues . Horm. Res. . 50 Suppl 2 . 7–14 . 1998 . 2 . 9721586 . 10.1159/000053118 . 72456840 .
• Chen M, Marinkovich MP, Jones JC, etal . NC1 domain of type VII collagen binds to the beta3 chain of laminin 5 via a unique subdomain within the fibronectin-like repeats . J. Invest. Dermatol. . 112 . 2 . 177–83 . 1999 . 9989793 . 10.1046/j.1523-1747.1999.00491.x . free .
• Miller KA, Chung J, Lo D, etal . Inhibition of laminin-5 production in breast epithelial cells by overexpression of p300 . J. Biol. Chem. . 275 . 11 . 8176–82 . 2000 . 10713141 . 10.1074/jbc.275.11.8176 . free .
• Olsen J, Lefebvre O, Fritsch C, etal . Involvement of activator protein 1 complexes in the epithelium-specific activation of the laminin gamma2-chain gene promoter by hepatocyte growth factor (scatter factor) . Biochem. J. . 347 . Pt 2 . 407–17 . 2001 . 10749670 . 10.1042/0264-6021:3470407 . 1220973 .
• Hirosaki T, Mizushima H, Tsubota Y, etal . Structural requirement of carboxyl-terminal globular domains of laminin alpha 3 chain for promotion of rapid cell adhesion and migration by laminin-5 . J. Biol. Chem. . 275 . 29 . 22495–502 . 2000 . 10801807 . 10.1074/jbc.M001326200 . free .
• Amano S, Scott IC, Takahara K, etal . Bone morphogenetic protein 1 is an extracellular processing enzyme of the laminin 5 gamma 2 chain . J. Biol. Chem. . 275 . 30 . 22728–35 . 2000 . 10806203 . 10.1074/jbc.M002345200 . free .
• Takizawa Y, Pulkkinen L, Chao SC, etal . Mutation report: complete paternal uniparental isodisomy of chromosome 1: a novel mechanism for Herlitz junctional epidermolysis bullosa . J. Invest. Dermatol. . 115 . 2 . 307–11 . 2000 . 10951251 . 10.1046/j.1523-1747.2000.00052.x . free .
• Manda R, Kohno T, Niki T, etal . Differential expression of the LAMB3 and LAMC2 genes between small cell and non-small cell lung carcinomas . Biochem. Biophys. Res. Commun. . 275 . 2 . 440–5 . 2000 . 10964684 . 10.1006/bbrc.2000.3331 .
• Spirito F, Chavanas S, Prost-Squarcioni C, etal . Reduced expression of the epithelial adhesion ligand laminin 5 in the skin causes intradermal tissue separation . J. Biol. Chem. . 276 . 22 . 18828–35 . 2001 . 11279058 . 10.1074/jbc.M100381200 . free .
• McArthur CP, Wang Y, Heruth D, Gustafson S . Amplification of extracellular matrix and oncogenes in tat-transfected human salivary gland cell lines with expression of laminin, fibronectin, collagens I, III, IV, c-myc and p53 . Arch. Oral Biol. . 46 . 6 . 545–55 . 2001 . 11311202 . 10.1016/S0003-9969(01)00014-0 .

Notes and References

1. Kallunki P, Sainio K, Eddy R, Byers M, Kallunki T, Sariola H, Beck K, Hirvonen H, Shows TB, Tryggvason K . A truncated laminin chain homologous to the B2 chain: structure, spatial expression, and chromosomal assignment . J Cell Biol . 119 . 3 . 679–93 . Nov 1992 . 1383240 . 2289671 . 10.1083/jcb.119.3.679 .
2. Web site: Entrez Gene: LAMC2 laminin, gamma 2.