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Fibronectin matrix formation
Stable Identifier
R-HSA-1566977
DOI
10.3180/REACT_160131.1
Type
Pathway
Species
Homo sapiens
Compartment
extracellular region
ReviewStatus
5/5
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Extracellular matrix organization (Homo sapiens)
Fibronectin matrix formation (Homo sapiens)
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Fibronectin (FN1) is found in the extracellular matrix (ECM) of all cells as linear and branched networks that surround and connect neighbouring cells (Singh et al. 2010). Prior to matrix formation FN1 exists as a protein dimer. Often the two peptide chains represent differentially-spliced variants. The chains are linked by a pair of C-terminal disulfide bonds which are essential for subsequent multimerization (Schwarzbaur 1991). FN1 monomers have a molecular weight of 230-270 kDa depending on alternative splicing and contain three types of repeating unit, I, II, and III. I and II are stabilized by intra-chain disulfide bonds. The absence of disulfide bonds in type III modules allows them to partially unfold under applied force (Erickson 2002). Three regions of variable splicing occur along the length of the FN1 monomer (Mao & Schwarzbauer 2005). One or both of the 'extra' type III modules EIIIA and EIIIB may be present in cellular FN1, but never in plasma FN1. A variable (V) region exists between the 14th and 15th type III module. This contains the binding site for alpha4 beta1 and alpha4beta7 integrins. It is present in most cellular FN1, occasionally in plasma FN1. The modules are arranged into several functional and protein-binding domains. There are four FN1-binding domains (Mao & Schwarzbauer 2005). One of these domains (I1-5), referred to as the 'assembly domain', is required for the initiation of FN1 matrix assembly. Modules III9-10 correspond to the 'cell-binding domain' of FN1. The Arg-Gly-Asp (RGD) integrin binding sequence located in III10 is the primary site of FN1 to cell attachment, mediated predominantly by alpha5 beta1 and alphaV beta3 integrins. The 'synergy site' in III9 modulates FN1's association with alpha5 beta1 integrins. FN1 also contains interaction domains for fibrin (I1-5, I10-12), collagen (I6-9, II1-2), fibulin-1 (III13-14), heparin, syndecan (III12-14) and fibrillin-1 (I6-9) (Mao & Schwartzbauer 2005, Sabatier et al. 2009).
FN1 dimer binding to alpha5beta1 integrin stimulates self-association. Binding is thought to lead to a conformational change in FN1 that triggers the addition of further FN1 dimers (Singh et al. 2010). I1-5 functions as a unit that is the primary FN1 matrix assembly domain (Sottile et al. 1991) but other units are likely to be involved (Singh et al. 2010), the process is not fully understood.
Several ECM proteins appear to require the FN1 matrix for their own assembly. Fibrillin-1 containing microfibrils are formed when fibrillin-1 multimers bind to the FN1 matrix (Sabatier et al. 2009). FN1 polymerization promotes the deposition of type I and type III collagen (Sottile and Hocking 2002, Velling et al. 2002). Inhibition of FN1 polymerization increases its turnover and a concomitant loss of collagen types I and III from the ECM (Sottile and Hocking 2002, Sottile et al. 2007). FN1 is regulated by matrix metalloproteinases, particularly MMP14 (Shi & Sottile 2011).
Literature References
PubMed ID
Title
Journal
Year
20690820
Assembly of fibronectin extracellular matrix
Singh, P
,
Schwarzbauer, JE
,
Carraher, C
Annu. Rev. Cell Dev. Biol.
2010
Participants
Events
FN1 dimerizes
(Homo sapiens)
Integrin alpha5beta1 binds FN1 dimer
(Homo sapiens)
FN1 aggregation
(Homo sapiens)
Participates
as an event of
Extracellular matrix organization (Homo sapiens)
Event Information
Go Biological Process
extracellular matrix organization (0030198)
Orthologous Events
Fibronectin matrix formation (Bos taurus)
Fibronectin matrix formation (Caenorhabditis elegans)
Fibronectin matrix formation (Canis familiaris)
Fibronectin matrix formation (Dictyostelium discoideum)
Fibronectin matrix formation (Gallus gallus)
Fibronectin matrix formation (Mus musculus)
Fibronectin matrix formation (Rattus norvegicus)
Fibronectin matrix formation (Sus scrofa)
Fibronectin matrix formation (Xenopus tropicalis)
Authored
Jupe, S (2011-07-12)
Reviewed
Reinhardt, DP (2013-02-08)
Created
Jupe, S (2011-09-06)
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