Integrin alpha L explained

Integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide), also known as ITGAL, is a protein that in humans is encoded by the ITGAL gene.^[1] CD11a functions in the immune system. It is involved in cellular adhesion and costimulatory signaling. It is the target of the drug efalizumab.

Function

ITGAL gene encodes the integrin alpha L chain. Integrins are heterodimeric integral membrane proteins composed of an alpha chain and a beta chain. This I-domain containing alpha integrin combines with the beta 2 chain (ITGB2) to form the integrin lymphocyte function-associated antigen-1 (LFA-1), which is expressed in all leukocytes. LFA-1 plays a central role in leukocyte intercellular adhesion through interactions with its ligands, ICAMs 1-3 (intercellular adhesion molecules 1 through 3), and also functions in lymphocyte costimulatory signaling.^[2]

CD11a is one of the two components, along with CD18, which form lymphocyte function-associated antigen-1.

Efalizumab acts as an immunosuppressant by binding to CD11a but was withdrawn in 2009 because it was associated with severe side effects.

Interactions

CD11a has been shown to interact with ICAM-1.^{[3] [4] [5]}

See also

• CD11c
• integrin
• leukocyte adhesion deficiency
• Cluster of differentiation

Further reading

• Lub M, van Kooyk Y, Figdor CG . Ins and outs of LFA-1. . Immunol. Today . 16 . 10 . 479–83 . 1995 . 7576051 . 10.1016/0167-5699(95)80031-X .
• Dickeson SK, Santoro SA . Ligand recognition by the I domain-containing integrins. . Cell. Mol. Life Sci. . 54 . 6 . 556–66 . 1998 . 9676575 . 10.1007/s000180050184 . 9775686 . 11147323 .
• Porter JC, Hogg N . Integrins take partners: cross-talk between integrins and other membrane receptors. . Trends Cell Biol. . 8 . 10 . 390–6 . 1999 . 9789327 . 10.1016/S0962-8924(98)01344-0 .
• Giblin PA, Lemieux RM . LFA-1 as a key regulator of immune function: approaches toward the development of LFA-1-based therapeutics. . Curr. Pharm. Des. . 12 . 22 . 2771–95 . 2006 . 16918410 . 10.2174/138161206777947731 .
• Maurer D, Holter W, Majdic O, Fischer GF, Knapp W . CD27 expression by a distinct subpopulation of human B lymphocytes. . Eur. J. Immunol. . 20 . 12 . 2679–84 . 1991 . 1702722 . 10.1002/eji.1830201223 . 9794163 .
• Howard E. Gendelman . Kalter DC, Gendelman HE, Meltzer MS . Inhibition of human immunodeficiency virus infection in monocytes by monoclonal antibodies against leukocyte adhesion molecules. . Immunol. Lett. . 30 . 2 . 219–27 . 1992 . 1757107 . 10.1016/0165-2478(91)90029-A .
• Alvarez V, Pulido R, Campanero MR, Paraiso V, de Landázuri MO, Sánchez-Madrid F . Differentially regulated cell surface expression of leukocyte adhesion receptors on neutrophils. . Kidney Int. . 40 . 5 . 899–905 . 1992 . 1762294 . 10.1038/ki.1991.291 . free .
• Valentin A, Lundin K, Patarroyo M, Asjö B . The leukocyte adhesion glycoprotein CD18 participates in HIV-1-induced syncytia formation in monocytoid and T cells. . J. Immunol. . 144 . 3 . 934–7 . 1990 . 10.4049/jimmunol.144.3.934 . 1967280 . free .
• Larson RS, Corbi AL, Berman L, Springer T . Primary structure of the leukocyte function-associated molecule-1 alpha subunit: an integrin with an embedded domain defining a protein superfamily . J. Cell Biol. . 108 . 2 . 703–12 . 1989 . 2537322 . 2115430 . 10.1083/jcb.108.2.703 .
• Hildreth JE, Orentas RJ . Involvement of a leukocyte adhesion receptor (LFA-1) in HIV-induced syncytium formation . Science . 244 . 4908 . 1075–8 . 1989 . 2543075 . 10.1126/science.2543075 . 1989Sci...244.1075H .
• Sanders ME, Makgoba MW, Sharrow SO, Stephany D, Springer TA, Young HA, Shaw S . Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production . J. Immunol. . 140 . 5 . 1401–7 . 1988 . 10.4049/jimmunol.140.5.1401 . 2894392 . free .
• Corbi AL, Larson RS, Kishimoto TK, Springer TA, Morton CC . Chromosomal location of the genes encoding the leukocyte adhesion receptors LFA-1, Mac-1 and p150,95. Identification of a gene cluster involved in cell adhesion . J. Exp. Med. . 167 . 5 . 1597–607 . 1988 . 3284962 . 2188934 . 10.1084/jem.167.5.1597 .
• te Velde AA, Keizer GD, Figdor CG . Differential function of LFA-1 family molecules (CD11 and CD18) in adhesion of human monocytes to melanoma and endothelial cells . Immunology . 61 . 3 . 261–7 . 1987 . 3301632 . 1453405 .
• Qu A, Leahy DJ . Crystal structure of the I-domain from the CD11a/CD18 (LFA-1, alpha L beta 2) integrin . Proc. Natl. Acad. Sci. U.S.A. . 92 . 22 . 10277–81 . 1995 . 7479767 . 40779 . 10.1073/pnas.92.22.10277 . 1995PNAS...9210277Q . free .
• Turner ML, McIlwaine K, Anthony RS, Parker AC . Differential expression of cell adhesion molecules by human hematopoietic progenitor cells from bone marrow and mobilized adult peripheral blood . Stem Cells . 13 . 3 . 311–6 . 1995 . 7542116 . 10.1002/stem.5530130312 . 21373771 .
• Marzusch K, Ruck P, Geiselhart A, Handgretinger R, Dietl JA, Kaiserling E, Horny HP, Vince G, Redman CW . Distribution of cell adhesion molecules on CD56++, CD3-, CD16- large granular lymphocytes and endothelial cells in first-trimester human decidua . Hum. Reprod. . 8 . 8 . 1203–8 . 1993 . 7691868 . 10.1093/oxfordjournals.humrep.a138229.
• Capobianchi MR, Ameglio F, Cordiali Fei P, Castilletti C, Mercuri F, Fais S, Dianzani F . Coordinate induction of interferon alpha and gamma by recombinant HIV-1 glycoprotein 120 . AIDS Res. Hum. Retroviruses . 9 . 10 . 957–62 . 1994 . 7904170 . 10.1089/aid.1993.9.957 .
• Berman PW, Nakamura GR . Adhesion mediated by intercellular adhesion molecule 1 attenuates the potency of antibodies that block HIV-1 gp160-dependent syncytium formation . AIDS Res. Hum. Retroviruses . 10 . 5 . 585–93 . 1994 . 7917519 . 10.1089/aid.1994.10.585 .
• Chirmule N, Oyaizu N, Saxinger C, Pahwa S . Nef protein of HIV-1 has B-cell stimulatory activity . AIDS . 8 . 6 . 733–4 . 1994 . 8086129 . 10.1097/00002030-199406000-00002 . 36774740 .

External links

• • ITGAL Info with links in the Cell Migration Gateway

Notes and References

1. Web site: NCBI.
2. Web site: Entrez Gene: ITGAL integrin, alpha L (antigen CD11A (p180), lymphocyte function-associated antigen 1; alpha polypeptide).
3. Lu C, Takagi J, Springer TA . Association of the membrane proximal regions of the alpha and beta subunit cytoplasmic domains constrains an integrin in the inactive state . J. Biol. Chem. . 276 . 18 . 14642–8 . May 2001 . 11279101 . 10.1074/jbc.M100600200 . free .
4. Shimaoka M, Xiao T, Liu JH, Yang Y, Dong Y, Jun CD, McCormack A, Zhang R, Joachimiak A, Takagi J, Wang JH, Springer TA . Structures of the alpha L I domain and its complex with ICAM-1 reveal a shape-shifting pathway for integrin regulation . Cell . 112 . 1 . 99–111 . Jan 2003 . 12526797 . 10.1016/S0092-8674(02)01257-6 . 4372089.
5. Yusuf-Makagiansar H, Makagiansar IT, Hu Y, Siahaan TJ . Synergistic inhibitory activity of alpha- and beta-LFA-1 peptides on LFA-1/ICAM-1 interaction . Peptides . 22 . 12 . 1955–62 . Dec 2001 . 11786177 . 10.1016/S0196-9781(01)00546-0 . 54343441 .