Integrin alpha5beta1 binds FN1 dimer

Stable Identifier
Reaction [binding]
Homo sapiens
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Alpha5beta1 integrin was the first integrin shown to bind fibronectin (FN1). Unlike other FN1-binding integrins it is a specialist at this task. In solution FN1 occurs as a dimer. Binding to alpha5beta1 integrin stimulates FN1 self-association; blocking the RGD-cell binding domain of FN1 blocks fibril formation (Fogerty et al. 1990). FN1 binding is believed to induce integrin clustering, which promotes FN1-FN1 interactions. Integrin clustering is mediated by association between integrins and intracellular actin stress fibers (Calderwood et al. 2000). Binding of integrins to each of the monomers in the FN1 dimer pair is thought to trigger a conformational change in FN1 that exposes 'cryptic' FN1 binding sites that allow additional fibronectin dimers to bind without the requirement for pre-association with integrins (Singh et al. 2010). This non-covalent interaction may involve interactions with fibrillin (Ohashi & Erickson 2009). I1-5 functions as a unit that is the primary FN matrix assembly domain (Sottile et al. 1991) but other units are likely to be involved (Singh et al. 2010). Other integrins able to bind FN1 include alphaIIbBeta3, which is highly expressed on platelets where it predominantly binds fibrinogen leading to thrombus formation but also binds FN1 (Savage et al. 1996). Alpha4beta1 mediates cell-cell contacts and cell-matrix contacts through the ligands VCAM-1 and FN1, respectively (Humphries et al. 1995). Integrins alpha3beta1, alpha4beta7, alphaVbeta1, 3 (Johansson et al. 1997), 6 (Busk et al. 1992) and alpha8beta1 (Muller et al. 1995, Farias et al. 2005) are all able to bind FN1.

Tenacious binding of free fibronectin to cells leads to enhanced fibronectin matrix assembly and the formation of a polymerized fibronectin "cocoon" around the cells. This process is enhanced in the presence of CEACAM molecules.

Literature References
PubMed ID Title Journal Year
8314844 The alpha v beta 1 integrin functions as a fibronectin receptor but does not support fibronectin matrix assembly and cell migration on fibronectin

Bauer, JS, Juliano, RL, Ruoslahti, E, Morla, AO, Vuori, K, Zhang, Z

J Cell Biol 1993
15721307 Integrin alpha8beta1-fibronectin interactions promote cell survival via PI3 kinase pathway

Schnapp, LM, Lu, M, Farias, E, Li, X

Biochem Biophys Res Commun 2005
16258728 beta 1 integrin function in vivo: adhesion, migration and more

Fassler, R, Brakebusch, C

Cancer Metastasis Rev 2005
17167768 GPI-anchored CEA family glycoproteins CEA and CEACAM6 mediate their biological effects through enhanced integrin alpha5beta1-fibronectin interaction

Zhai, AB, Camacho-Leal, P, Stanners, CP, Ordonez, C, Fan, MM, Demarte, L

J Cell Physiol 2007
This event is regulated
Orthologous Events
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