Fibronectin

Source: Wikipedia, the free encyclopedia.

FN1
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl

ENSG00000115414

ENSMUSG00000026193

UniProt

P02751

P11276

RefSeq (mRNA)
RefSeq (protein)
Location (UCSC)Chr 2: 215.36 – 215.44 MbChr 1: 71.62 – 71.69 Mb
PubMed search[3][4]
Wikidata
View/Edit HumanView/Edit Mouse
The modular structure of fibronectin and its binding domains

Fibronectin is a high-

syndecans
).

Fibronectin exists as a

isoforms
.

Two types of fibronectin are present in

vertebrates:[6]

Fibronectin plays a major role in

pathologies, including cancer, arthritis, and fibrosis.[7][8]

Structure

Fibronectin exists as a protein dimer, consisting of two nearly identical

β-sheets resulting in a Beta-sandwich; however, type I and type II are stabilized by intra-chain disulfide bonds, while type III modules do not contain any disulfide bonds. The absence of disulfide bonds in type III modules allows them to partially unfold under applied force.[11]

Three regions of variable

α4β1
integrins. It is present in most cellular fibronectin, but only one of the two subunits in a plasma fibronectin dimer contains a V-region sequence.

The modules are arranged into several functional and

fibulin-1-binding (III13–14), heparin-binding and syndecan-binding (III12–14).[9]

Function

Fibronectin has numerous functions that ensure the normal functioning of

organs and tissues
of an organism.

Fibronectin plays a crucial role in

α4β1 integrin
binding. These fragments of fibronectin are believed to enhance the binding of α4β1 integrin-expressing cells, allowing them to adhere to and forcefully contract the surrounding matrix.

Fibronectin is necessary for

mesodermal patterning and inhibits gastrulation.[16]

Fibronectin is also found in normal human saliva, which helps prevent

oral cavity and pharynx by pathogenic bacteria.[17]

Matrix assembly

fibrils then begin to form between adjacent cells. As matrix assembly proceeds, the soluble fibrils are converted into larger insoluble fibrils that comprise the extracellular matrix
.

Fibronectin's shift from

soluble to insoluble fibrils proceeds when cryptic fibronectin-binding sites are exposed along the length of a bound fibronectin molecule. Cells are believed to stretch fibronectin by pulling on their fibronectin-bound integrin receptors. This force partially unfolds the fibronectin ligand, unmasking cryptic fibronectin-binding sites and allowing nearby fibronectin molecules to associate. This fibronectin-fibronectin interaction enables the soluble, cell-associated fibrils to branch and stabilize into an insoluble fibronectin matrix
.

A transmembrane protein, CD93, has been shown to be essential for fibronectin matrix assembly (fibrillogenesis) in human dermal blood endothelial cells.[19] As a consequence, knockdown of CD93 in these cells resulted in the disruption of the fibronectin fibrillogenesis. Moreover, the CD93 knockout mice retinas displayed disrupted fibronectin matrix at the retinal sprouting front.[19]

Role in cancer

Several morphological changes has been observed in

integrins.[20]

Fibronectin has been implicated in

anticancer drugs
.

Fibronectin 1 acts as a potential biomarker for radioresistance[22] and for pan-cancer prognosis.[23]

FN1-FGFR1 fusion is frequent in phosphaturic mesenchymal tumours.[24][25]

Role in wound healing

Fibronectin has profound effects on wound healing, including the formation of proper substratum for migration and growth of cells during the development and organization of granulation tissue, as well as remodeling and resynthesis of the connective tissue matrix.[26] The biological significance of fibronectin in vivo was studied during the mechanism of wound healing.[26] Plasma fibronectin levels are decreased in acute inflammation or following surgical trauma and in patients with disseminated intravascular coagulation.[27]

Fibronectin is located in the extracellular matrix of embryonic and adult tissues (not in the

reticulin). An in vitro study with native collagen demonstrated that fibronectin binds to type III collagen rather than other types.[30]

In vivo vs in vitro

Plasma fibronectin, which is synthesized by

N-ethylmaleimide prevents binding to cell layers. Tryptic cleavage patterns of multimeric fibronectin do not reveal the disulfide-bonded fragments that would be expected if multimerization involved one or both of the free sulfhydryls. The free sulfhydryls of fibronectin are not required for the binding of fibronectin to the cell layer or for its subsequent incorporation into the extracellular matrix. Disulfide-bonded multimerization of fibronectin in the cell layer occurs by disulfide bond exchange in the disulfide-rich amino-terminal one-third of the molecule.[32]

Fibronectin genetic variation as a protective factor against Alzheimer's disease

A specific genetic variation in Fibronectin gene was shown to reduce the risk of developing Alzheimer's disease in a multicenter, multiethnic genetic epidemiology and functional genomics study. This effect is believed to be through enhancing the brain's ability to clear the toxic waste and protein accummulation through blood-brain-barrier. [33]


Interactions

Besides integrin, fibronectin binds to many other host and non-host molecules. For example, it has been shown to interact with proteins such fibrin, tenascin, TNF-α, BMP-1, rotavirus NSP-4, and many fibronectin-binding proteins from bacteria (like FBP-A; FBP-B on the N-terminal domain), as well as the glycosaminoglycan, heparan sulfate.

Fibronectin has been shown to

interact
with:

See also

References

  1. ^ a b c GRCh38: Ensembl release 89: ENSG00000115414 – Ensembl, May 2017
  2. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000026193 – Ensembl, May 2017
  3. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. PMID 17974429. Archived from the original
    on February 9, 2022.
  6. ^
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  7. PMID 18451144
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  8. PMID 31819923
    .
  9. ^
    PMID 16061370
    .
  10. ^ Sitterley G. "Fibronectin". Sigma Aldrich.
  11. S2CID 7052723
    .
  12. PMID 9398676
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  13. S2CID 28645109
    .
  14. PMID 15992798
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  15. PMID 8306876
    .
  16. S2CID 2640979
    .
  17. PMID 3305363
    .
  18. S2CID 16975447
    .
  19. ^
    PMID 29763414
    .
  20. ISBN 978-0-387-97050-9
    .
  21. PMID 16397245
    .
  22. PMID 20930522
    .
  23. PMID 36329531
    .
  24. PMID 26759148
    .
  25. S2CID 9887919
    .
  26. ^
    PMID 7240787
    .
  27. PMID 1002003
    .
  28. PMID 1158872
    .
  29. PMID 56335
    .
  30. PMID 567240
    .
  31. PMID 6339502
    .
  32. ^
    PMID 6480605
    .
  33. PMID 38598053
    .
  34. PMID 1730778
    .
  35. PMID 7963647
    .
  36. PMID 9169408
    .
  37. PMID 2531657
    .
  38. PMID 12127836
    .
  39. PMID 11344214
    .
  40. PMID 7499434
    .
  41. PMID 18276110
    .

Further reading

External links
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