The fate of internalized α5 integrin is regulated by matrix-capable fibronectin

Henry C. Hsia, Mohan R. Nair, Siobhan Corbett

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

Conclusions Our data demonstrate that α5 integrin turnover is dependent on fibronectin matrix assembly, where the absence of matrix-capable fibronectin in the extracellular space targets the internalized receptor for rapid degradation. These findings have important implications for understanding tissue-remodeling processes found in wound repair and tumor invasion.

Background: Assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. Although it is well established that fibronectin is the primary ligand for α5β1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized.

Materials and methods To evaluate the effect of fibronectin matrix on the fate of internalized α5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of α5 after exposure to exogenous fibronectin.

Results: In the absence of matrix-capable fibronectin dimer, levels of internalized α5 decreased rapidly over time. This correlated with a decline in total cellular α5 and was associated with the ubiquitination of α5 integrin. In contrast, internalized and total cellular α5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized α5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the α5 cytoplasmic tail.

Original languageEnglish (US)
Pages (from-to)268-279
Number of pages12
JournalJournal of Surgical Research
Volume191
Issue number2
DOIs
StatePublished - Oct 1 2014

Fingerprint

Fibronectins
Integrins
Ubiquitination
Extracellular Space
Cricetulus
Lysine
Tail
Ovary
Embryonic Structures
Fibroblasts
Ligands
Wounds and Injuries

All Science Journal Classification (ASJC) codes

  • Surgery

Keywords

  • Endocytosis
  • Extracellular matrix
  • Fibronectin
  • Matrix assembly
  • Tissue remodeling
  • α5 integrin

Cite this

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title = "The fate of internalized α5 integrin is regulated by matrix-capable fibronectin",
abstract = "Conclusions Our data demonstrate that α5 integrin turnover is dependent on fibronectin matrix assembly, where the absence of matrix-capable fibronectin in the extracellular space targets the internalized receptor for rapid degradation. These findings have important implications for understanding tissue-remodeling processes found in wound repair and tumor invasion.Background: Assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. Although it is well established that fibronectin is the primary ligand for α5β1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized.Materials and methods To evaluate the effect of fibronectin matrix on the fate of internalized α5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of α5 after exposure to exogenous fibronectin.Results: In the absence of matrix-capable fibronectin dimer, levels of internalized α5 decreased rapidly over time. This correlated with a decline in total cellular α5 and was associated with the ubiquitination of α5 integrin. In contrast, internalized and total cellular α5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized α5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the α5 cytoplasmic tail.",
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The fate of internalized α5 integrin is regulated by matrix-capable fibronectin. / Hsia, Henry C.; Nair, Mohan R.; Corbett, Siobhan.

In: Journal of Surgical Research, Vol. 191, No. 2, 01.10.2014, p. 268-279.

Research output: Contribution to journalArticle

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T1 - The fate of internalized α5 integrin is regulated by matrix-capable fibronectin

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AU - Nair, Mohan R.

AU - Corbett, Siobhan

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N2 - Conclusions Our data demonstrate that α5 integrin turnover is dependent on fibronectin matrix assembly, where the absence of matrix-capable fibronectin in the extracellular space targets the internalized receptor for rapid degradation. These findings have important implications for understanding tissue-remodeling processes found in wound repair and tumor invasion.Background: Assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. Although it is well established that fibronectin is the primary ligand for α5β1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized.Materials and methods To evaluate the effect of fibronectin matrix on the fate of internalized α5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of α5 after exposure to exogenous fibronectin.Results: In the absence of matrix-capable fibronectin dimer, levels of internalized α5 decreased rapidly over time. This correlated with a decline in total cellular α5 and was associated with the ubiquitination of α5 integrin. In contrast, internalized and total cellular α5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized α5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the α5 cytoplasmic tail.

AB - Conclusions Our data demonstrate that α5 integrin turnover is dependent on fibronectin matrix assembly, where the absence of matrix-capable fibronectin in the extracellular space targets the internalized receptor for rapid degradation. These findings have important implications for understanding tissue-remodeling processes found in wound repair and tumor invasion.Background: Assembly of fibronectin matrices is associated with integrin receptor turnover and is an important determinant of tissue remodeling. Although it is well established that fibronectin is the primary ligand for α5β1 receptor, the relationship between fibronectin matrix assembly and the fate of internalized α5 integrin remains poorly characterized.Materials and methods To evaluate the effect of fibronectin matrix on the fate of internalized α5 integrin, fibronectin-null Chinese hamster ovary and mouse embryo fibroblast cells were used to track the fate of α5 after exposure to exogenous fibronectin.Results: In the absence of matrix-capable fibronectin dimer, levels of internalized α5 decreased rapidly over time. This correlated with a decline in total cellular α5 and was associated with the ubiquitination of α5 integrin. In contrast, internalized and total cellular α5 protein levels were maintained when matrix-capable fibronectin was present in the extracellular space. Further, we show that ubiquitination and degradation of internalized α5 integrin in the absence of fibronectin require the presence of two specific lysine residues in the α5 cytoplasmic tail.

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