Integrin beta 1 explained

Integrin beta-1 (ITGB1), also known as CD29, is a cell surface receptor that in humans is encoded by the ITGB1 gene.[1] This integrin associates with integrin alpha 1 and integrin alpha 2 to form integrin complexes which function as collagen receptors. It also forms dimers with integrin alpha 3 to form integrin receptors for netrin 1 and reelin. These and other integrin beta 1 complexes have been historically known as very late activation (VLA) antigens.

Integrin beta 1 is expressed as at least four different isoforms. In cardiac muscle and skeletal muscle, the integrin beta-1D isoform is specifically expressed, and localizes to costameres, where it aids in the lateral force transmission from the Z-discs to the extracellular matrix. Abnormal levels of integrin beta-1D have been found in limb girdle muscular dystrophy and polyneuropathy.

Structure

Integrin beta-1 can exist as different isoforms via alternative splicing. Six alternatively spliced variants have been found for this gene which encode five proteins with alternate C-termini.[2] Integrin receptors exist as heterodimers, and greater than 20 different integrin heterodimeric receptors have been described. All integrins, alpha and beta forms, have large extracellular and short intracellular domains.[3] The cytoplasmic domain of integrin beta-1 binds to the actin cytoskeleton.[4] Integrin beta-1 is the most abundant beta-integrin expressed and associates with at least 10 different integrin-alpha subunits.[3]

Function

Integrin family members are membrane receptors involved in cell adhesion and recognition in a variety of processes including embryogenesis, hemostasis, tissue repair, immune response and metastatic diffusion of tumor cells.[3] Integrins link the actin cytoskeleton with the extracellular matrix and they transmit signals bidirectionally between the extracellular matrix and cytoplasmic domains.[5] [6] Beta-integrins are primarily responsible for targeting integrin dimers to the appropriate subcellular locations, which in adhesive cells is mainly focal adhesions.[4] [7] Integrin beta-1 mutants lose the ability to target to sites of focal adhesions.[8] [9]

Three novel isoforms of integrin beta-1 have been identified, termed beta-1B, beta-1C and beta-1D. Integrin beta-1B is transcribed when the proximal 26 amino acids of the cytoplasmic domain in exon 6 are retained and then succeeded by a 12 amino acid stretch from an adjacent intronic region.[10] The integrin beta-1B isoform appears to act as a dominant negative in that it inhibits cell adhesion.[11] A second integrin beta-1 isoform, termed beta-1C, was described to have an additional 48 amino acids appended to the 26 amino acids in the cytoplasmic domain;[12] the function of this isoform was an inhibitory one on DNA synthesis in the G1 phase of the cell cycle.[13] The third isoform, termed beta-1D, is a striated muscle-specific isoform, which replaces the canonical beta-1A isoform in cardiac and skeletal muscle cells. This isoform is produced from splicing into a novel additional exon between exons 6 and 7. The cytoplasmic domain of integrin beta-1D replaces the distal 21 amino acids (present in integrin beta-1A) with an alternative stretch of 24 amino acids (13 unique).[14] [15]

Integrin beta-1D appears to be developmentally regulated during myofibrilogenesis,[15] appearing immediately following the fusion of myoblasts in C2C12 cell with rising levels throughout myofibrillar differentiation.[16] Integrin beta-1D is specifically localized to costameres and intercalated discs of cardiac muscle and costameres, myotendinous junctions and neuromuscular junctions of skeletal muscle, and it appears to function in general like other integrins, as the clustering of beta-1D integrins on the surface of CHO cells resulted in tyrosine phosphorylation of pp125FAK and induced mitogen-activated protein kinase activation.[16]

Clinical significance

In patients with limb girdle muscular dystrophy, type 2C, beta-1D integrin has been shown to be severely reduced in skeletal muscle biopsies, coordinate with a reduction in alpha 7B-integrin and filamin 2.[17]

In patients with sensitive-motor polyneuropathy, levels of integrin alpha-7B, integrin beta-1D and agrin were significantly reduced nearly to undetectable levels; and this corresponded with lower mRNA levels.[18]

Interactions

CD29 has been shown to interact with

Further reading

Notes and References

  1. Goodfellow PJ, Nevanlinna HA, Gorman P, Sheer D, Lam G, Goodfellow PN . Assignment of the gene encoding the beta-subunit of the human fibronectin receptor (beta-FNR) to chromosome 10p11.2 . Annals of Human Genetics . 53 . Pt 1 . 15–22 . Jan 1989 . 2524991 . 10.1111/j.1469-1809.1989.tb01118.x . 36485270 .
  2. Web site: Entrez Gene: ITGB1 integrin, beta 1 (fibronectin receptor, beta polypeptide, antigen CD29 includes MDF2, MSK12).
  3. Hynes RO . Integrins: versatility, modulation, and signaling in cell adhesion . Cell . 69 . 1 . 11–25 . Apr 1992 . 1555235 . 10.1016/0092-8674(92)90115-s. 32774108 .
  4. Sastry SK, Horwitz AF . Integrin cytoplasmic domains: mediators of cytoskeletal linkages and extra- and intracellular initiated transmembrane signaling . Current Opinion in Cell Biology . 5 . 5 . 819–31 . Oct 1993 . 8240826 . 10.1016/0955-0674(93)90031-k.
  5. Burridge K, Chrzanowska-Wodnicka M . Focal adhesions, contractility, and signaling . Annual Review of Cell and Developmental Biology . 12 . 463–518 . 1996 . 8970735 . 10.1146/annurev.cellbio.12.1.463 . 28558568 .
  6. Schwartz MA, Schaller MD, Ginsberg MH . Integrins: emerging paradigms of signal transduction . Annual Review of Cell and Developmental Biology . 11 . 549–99 . 1995 . 8689569 . 10.1146/annurev.cb.11.110195.003001 .
  7. LaFlamme SE, Akiyama SK, Yamada KM . Regulation of fibronectin receptor distribution . The Journal of Cell Biology . 117 . 2 . 437–47 . Apr 1992 . 1373145 . 10.1083/jcb.117.2.437 . 2289425.
  8. Akiyama SK, Yamada SS, Yamada KM, LaFlamme SE . Transmembrane signal transduction by integrin cytoplasmic domains expressed in single-subunit chimeras . The Journal of Biological Chemistry . 269 . 23 . 15961–4 . Jun 1994 . 10.1016/S0021-9258(17)33955-8 . 7515874 . free .
  9. Reszka AA, Hayashi Y, Horwitz AF . Identification of amino acid sequences in the integrin beta 1 cytoplasmic domain implicated in cytoskeletal association . The Journal of Cell Biology . 117 . 6 . 1321–30 . Jun 1992 . 1376731 . 10.1083/jcb.117.6.1321 . 2289496.
  10. Altruda F, Cervella P, Tarone G, Botta C, Balzac F, Stefanuto G, Silengo L . A human integrin beta 1 subunit with a unique cytoplasmic domain generated by alternative mRNA processing . Gene . 95 . 2 . 261–6 . Nov 1990 . 2249781 . 10.1016/0378-1119(90)90369-3.
  11. Balzac F, Retta SF, Albini A, Melchiorri A, Koteliansky VE, Geuna M, Silengo L, Tarone G . Expression of beta 1B integrin isoform in CHO cells results in a dominant negative effect on cell adhesion and motility . The Journal of Cell Biology . 127 . 2 . 557–65 . Oct 1994 . 7523423 . 10.1083/jcb.127.2.557 . 2120206. 2318/39410 .
  12. Languino LR, Ruoslahti E . An alternative form of the integrin beta 1 subunit with a variant cytoplasmic domain . The Journal of Biological Chemistry . 267 . 10 . 7116–20 . Apr 1992 . 10.1016/S0021-9258(19)50545-2 . 1551917 . free .
  13. Meredith J, Takada Y, Fornaro M, Languino LR, Schwartz MA . Inhibition of cell cycle progression by the alternatively spliced integrin beta 1C . Science . 269 . 5230 . 1570–2 . Sep 1995 . 7545312 . 10.1126/science.7545312. 1995Sci...269.1570M .
  14. Zhidkova NI, Belkin AM, Mayne R . Novel isoform of beta 1 integrin expressed in skeletal and cardiac muscle . Biochemical and Biophysical Research Communications . 214 . 1 . 279–85 . Sep 1995 . 7545396 . 10.1006/bbrc.1995.2285 .
  15. van der Flier A, Kuikman I, Baudoin C, van der Neut R, Sonnenberg A . A novel beta 1 integrin isoform produced by alternative splicing: unique expression in cardiac and skeletal muscle . FEBS Letters . 369 . 2–3 . 340–4 . Aug 1995 . 7544298 . 10.1016/0014-5793(95)00814-p. 86638879 . free .
  16. Belkin AM, Zhidkova NI, Balzac F, Altruda F, Tomatis D, Maier A, Tarone G, Koteliansky VE, Burridge K . Beta 1D integrin displaces the beta 1A isoform in striated muscles: localization at junctional structures and signaling potential in nonmuscle cells . The Journal of Cell Biology . 132 . 1–2 . 211–26 . Jan 1996 . 8567725 . 10.1083/jcb.132.1.211 . 2120711.
  17. Anastasi G, Cutroneo G, Trimarchi F, Santoro G, Bruschetta D, Bramanti P, Pisani A, Favaloro A . Evaluation of sarcoglycans, vinculin-talin-integrin system and filamin2 in alpha- and gamma-sarcoglycanopathy: an immunohistochemical study . International Journal of Molecular Medicine . 14 . 6 . 989–99 . Dec 2004 . 15547664 . 10.3892/ijmm.14.6.989 .
  18. Anastasi G, Cutroneo G, Santoro G, Arco A, Rizzo G, Bramanti P, Rinaldi C, Sidoti A, Amato A, Favaloro A . Costameric proteins in human skeletal muscle during muscular inactivity . Journal of Anatomy . 213 . 3 . 284–95 . Sep 2008 . 18537849 . 10.1111/j.1469-7580.2008.00921.x . 2732038.
  19. Otey CA, Pavalko FM, Burridge K . An interaction between alpha-actinin and the beta 1 integrin subunit in vitro . The Journal of Cell Biology . 111 . 2 . 721–9 . Aug 1990 . 2116421 . 10.1083/jcb.111.2.721 . 2116186.
  20. Otey CA, Vasquez GB, Burridge K, Erickson BW . Mapping of the alpha-actinin binding site within the beta 1 integrin cytoplasmic domain . The Journal of Biological Chemistry . 268 . 28 . 21193–7 . Oct 1993 . 10.1016/S0021-9258(19)36909-1 . 7691808 . free .
  21. Lozahic S, Christiansen D, Manié S, Gerlier D, Billard M, Boucheix C, Rubinstein E . CD46 (membrane cofactor protein) associates with multiple beta1 integrins and tetraspans . European Journal of Immunology . 30 . 3 . 900–7 . Mar 2000 . 10741407 . 10.1002/1521-4141(200003)30:3<900::AID-IMMU900>3.0.CO;2-X . free .
  22. Radford KJ, Thorne RF, Hersey P . CD63 associates with transmembrane 4 superfamily members, CD9 and CD81, and with beta 1 integrins in human melanoma . Biochemical and Biophysical Research Communications . 222 . 1 . 13–8 . May 1996 . 8630057 . 10.1006/bbrc.1996.0690 .
  23. Mazzocca A, Carloni V, Sciammetta S, Cordella C, Pantaleo P, Caldini A, Gentilini P, Pinzani M . Expression of transmembrane 4 superfamily (TM4SF) proteins and their role in hepatic stellate cell motility and wound healing migration . Journal of Hepatology . 37 . 3 . 322–30 . Sep 2002 . 12175627 . 10.1016/S0168-8278(02)00175-7 .
  24. Wixler V, Geerts D, Laplantine E, Westhoff D, Smyth N, Aumailley M, Sonnenberg A, Paulsson M . The LIM-only protein DRAL/FHL2 binds to the cytoplasmic domain of several alpha and beta integrin chains and is recruited to adhesion complexes . The Journal of Biological Chemistry . 275 . 43 . 33669–78 . Oct 2000 . 10906324 . 10.1074/jbc.M002519200 . free .
  25. van der Flier A, Kuikman I, Kramer D, Geerts D, Kreft M, Takafuta T, Shapiro SS, Sonnenberg A . Different splice variants of filamin-B affect myogenesis, subcellular distribution, and determine binding to integrin [beta] subunits . The Journal of Cell Biology . 156 . 2 . 361–76 . Jan 2002 . 11807098 . 2199218 . 10.1083/jcb.200103037 .
  26. Loo DT, Kanner SB, Aruffo A . Filamin binds to the cytoplasmic domain of the beta1-integrin. Identification of amino acids responsible for this interaction . The Journal of Biological Chemistry . 273 . 36 . 23304–12 . Sep 1998 . 9722563 . 10.1074/jbc.273.36.23304 . free .
  27. Serru V, Le Naour F, Billard M, Azorsa DO, Lanza F, Boucheix C, Rubinstein E . Selective tetraspan-integrin complexes (CD81/alpha4beta1, CD151/alpha3beta1, CD151/alpha6beta1) under conditions disrupting tetraspan interactions . The Biochemical Journal . 340 . Pt 1 . 103–11 . May 1999 . 10229664 . 1220227 . 10.1042/0264-6021:3400103 .
  28. Liliental J, Chang DD . Rack1, a receptor for activated protein kinase C, interacts with integrin beta subunit . The Journal of Biological Chemistry . 273 . 4 . 2379–83 . Jan 1998 . 9442085 . 10.1074/jbc.273.4.2379 . free .
  29. Chang DD, Wong C, Smith H, Liu J . ICAP-1, a novel beta1 integrin cytoplasmic domain-associated protein, binds to a conserved and functionally important NPXY sequence motif of beta1 integrin . The Journal of Cell Biology . 138 . 5 . 1149–57 . Sep 1997 . 9281591 . 2136751 . 10.1083/jcb.138.5.1149 .
  30. Chang DD, Hoang BQ, Liu J, Springer TA . Molecular basis for interaction between Icap1 alpha PTB domain and beta 1 integrin . The Journal of Biological Chemistry . 277 . 10 . 8140–5 . Mar 2002 . 11741908 . 10.1074/jbc.M109031200 . free .
  31. Hadari YR, Arbel-Goren R, Levy Y, Amsterdam A, Alon R, Zakut R, Zick Y . Galectin-8 binding to integrins inhibits cell adhesion and induces apoptosis . Journal of Cell Science . 113 . 13. 2385–97 . Jul 2000 . 10.1242/jcs.113.13.2385 . 10852818 .
  32. Poinat P, De Arcangelis A, Sookhareea S, Zhu X, Hedgecock EM, Labouesse M, Georges-Labouesse E . A conserved interaction between beta1 integrin/PAT-3 and Nck-interacting kinase/MIG-15 that mediates commissural axon navigation in C. elegans . Current Biology . 12 . 8 . 622–31 . Apr 2002 . 11967148 . 10.1016/S0960-9822(02)00764-9 . 9977605 . free . 2002CBio...12..622P .
  33. Fournier HN, Dupé-Manet S, Bouvard D, Lacombe ML, Marie C, Block MR, Albiges-Rizo C . Integrin cytoplasmic domain-associated protein 1alpha (ICAP-1alpha) interacts directly with the metastasis suppressor nm23-H2, and both proteins are targeted to newly formed cell adhesion sites upon integrin engagement . The Journal of Biological Chemistry . 277 . 23 . 20895–902 . Jun 2002 . 11919189 . 10.1074/jbc.M200200200 . free.
  34. Lee HS, Millward-Sadler SJ, Wright MO, Nuki G, Al-Jamal R, Salter DM . Activation of Integrin-RACK1/PKCalpha signalling in human articular chondrocyte mechanotransduction . Osteoarthritis and Cartilage . 10 . 11 . 890–7 . Nov 2002 . 12435334 . 10.1053/joca.2002.0842 . free .
  35. Parsons M, Keppler MD, Kline A, Messent A, Humphries MJ, Gilchrist R, Hart IR, Quittau-Prevostel C, Hughes WE, Parker PJ, Ng T . Site-directed perturbation of protein kinase C- integrin interaction blocks carcinoma cell chemotaxis . Molecular and Cellular Biology . 22 . 16 . 5897–911 . Aug 2002 . 12138200 . 133968 . 10.1128/MCB.22.16.5897-5911.2002 .
  36. Tapley P, Horwitz A, Buck C, Duggan K, Rohrschneider L . Integrins isolated from Rous sarcoma virus-transformed chicken embryo fibroblasts . Oncogene . 4 . 3 . 325–33 . Mar 1989 . 2468126 .
  37. Horwitz A, Duggan K, Buck C, Beckerle MC, Burridge K . Interaction of plasma membrane fibronectin receptor with talin--a transmembrane linkage . Nature . 320 . 6062 . 531–3 . 1986 . 2938015 . 10.1038/320531a0 . 1986Natur.320..531H . 4356748 .
  38. Tachibana I, Bodorova J, Berditchevski F, Zutter MM, Hemler ME . NAG-2, a novel transmembrane-4 superfamily (TM4SF) protein that complexes with integrins and other TM4SF proteins . The Journal of Biological Chemistry . 272 . 46 . 29181–9 . Nov 1997 . 9360996 . 10.1074/jbc.272.46.29181 . free .
  39. Han DC, Rodriguez LG, Guan JL . Identification of a novel interaction between integrin beta1 and 14-3-3beta . Oncogene . 20 . 3 . 346–57 . Jan 2001 . 11313964 . 10.1038/sj.onc.1204068 . 7405925 .

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