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
Regulation of the trafficking and the function of the metalloprotease ADAM10 by tetraspanins Available to Purchase
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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