By interacting directly with partner proteins and with one another, tetraspanins organize a network of interactions referred to as the tetraspanin web. ADAM10 (A Disintegrin And Metalloprotease 10), an essential membrane-anchored metalloprotease that cleaves off the ectodomain of a large variety of cell surface proteins including cytokines, adhesion molecules, the precursor of the β-amyloid peptide APP or Notch, has emerged as a major component of the tetraspanin web. Recent studies have shown that ADAM10 associates directly with all members (Tspan5, Tspan10, Tspan14, Tspan15, Tspan17 and Tspan33) of a subgroup of tetraspanins having eight cysteines in the large extracellular domain and referred to as TspanC8. All TspanC8 regulate ADAM10 exit from the endoplasmic reticulum, but differentially regulate its subsequent trafficking and its function, and have notably a different impact on Notch signaling. TspanC8 orthologs in invertebrates also regulate ADAM10 trafficking and Notch signaling. It may be possible to target TspanC8 tetraspanins to modulate in a tissue- or substrate-restricted manner ADAM10 function in pathologies such as cardiovascular diseases, cancer or Alzheimer's disease.
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Activating and inhibitory long non-coding RNAs of the NF-κβ canonical pathway. In this issue, Magagula et al. explore the lncRNAs that are directly involved in regulating innate immunity at various branches of the NF-κβ pathway, and also consider their potential diagnostic and therapeutic significance. For further details, see pages 953–962
Review Article|
July 07 2017
Regulation of the trafficking and the function of the metalloprotease ADAM10 by tetraspanins
Julien Saint-Pol;
Julien Saint-Pol
1Inserm, U935, F-94807 Villejuif, France
2Université Paris-Sud, Institut André Lwoff, F-94807 Villejuif, France
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Etienne Eschenbrenner;
Etienne Eschenbrenner
1Inserm, U935, F-94807 Villejuif, France
2Université Paris-Sud, Institut André Lwoff, F-94807 Villejuif, France
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Emmanuel Dornier;
Emmanuel Dornier
2Université Paris-Sud, Institut André Lwoff, F-94807 Villejuif, France
3Inserm, U1004, F-94807 Villejuif, France
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Claude Boucheix;
Claude Boucheix
1Inserm, U935, F-94807 Villejuif, France
2Université Paris-Sud, Institut André Lwoff, F-94807 Villejuif, France
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Stéphanie Charrin;
Stéphanie Charrin
1Inserm, U935, F-94807 Villejuif, France
2Université Paris-Sud, Institut André Lwoff, F-94807 Villejuif, France
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Eric Rubinstein
1Inserm, U935, F-94807 Villejuif, France
2Université Paris-Sud, Institut André Lwoff, F-94807 Villejuif, France
Correspondence: Eric Rubinstein (eric.rubinstein@inserm.fr)
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Publisher: Portland Press Ltd
Received:
February 01 2017
Revision Received:
March 15 2017
Accepted:
April 03 2017
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society
2017
Biochem Soc Trans (2017) 45 (4): 937–944.
Article history
Received:
February 01 2017
Revision Received:
March 15 2017
Accepted:
April 03 2017
Citation
Julien Saint-Pol, Etienne Eschenbrenner, Emmanuel Dornier, Claude Boucheix, Stéphanie Charrin, Eric Rubinstein; Regulation of the trafficking and the function of the metalloprotease ADAM10 by tetraspanins. Biochem Soc Trans 15 August 2017; 45 (4): 937–944. doi: https://doi.org/10.1042/BST20160296
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