Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10

Prox J, Willenbrock M, Weber S, Lehmann T, Schmidt-Arras D, Schwanbeck R, Saftig P, Schwake M (2012)
Cellular and Molecular Life Sciences 69(17): 2919-2932.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Prox, Johannes; Willenbrock, Michael; Weber, Silvio; Lehmann, Tobias; Schmidt-Arras, Dirk; Schwanbeck, Ralf; Saftig, Paul; Schwake, MichaelUniBi
Abstract / Bemerkung
A disintegrin and metalloproteinase10 (ADAM10) has been implicated as a major sheddase responsible for the ectodomain shedding of a number of important surface molecules including the amyloid precursor protein and cadherins. Despite a well-documented role of ADAM10 in health and disease, little is known about the regulation of this protease. To address this issue we conducted a split-ubiquitin yeast two-hybrid screen to identify membrane proteins that interact with ADAM10. The yeast experiments and co-immunoprecipitation studies in mammalian cell lines revealed tetraspanin15 (TSPAN15) to specifically associate with ADAM10. Overexpression of TSPAN15 or RNAi-mediated knockdown of TSPAN15 led to significant changes in the maturation process and surface expression of ADAM10. Expression of an endoplasmic reticulum (ER) retention mutant of TSPAN15 demonstrated an interaction with ADAM10 already in the ER. Pulse-chase experiments confirmed that TSPAN15 accelerates the ER-exit of the ADAM10–TSPAN15 complex and stabilizes the active form of ADAM10 at the cell surface. Importantly, TSPAN15 also showed the ability to mediate the regulation of ADAM10 protease activity exemplified by an increased shedding of N-cadherin and the amyloid precursor protein. In conclusion, our data show that TSPAN15 is a central modulator of ADAM10-mediated ectodomain shedding. Therapeutic manipulation of its expression levels may be an additional approach to specifically regulate the activity of the amyloid precursor protein alpha-secretase ADAM10.
Erscheinungsjahr
2012
Zeitschriftentitel
Cellular and Molecular Life Sciences
Band
69
Ausgabe
17
Seite(n)
2919-2932
ISSN
1420-682X
eISSN
1420-9071
Page URI
https://pub.uni-bielefeld.de/record/2953343

Zitieren

Prox J, Willenbrock M, Weber S, et al. Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cellular and Molecular Life Sciences. 2012;69(17):2919-2932.
Prox, J., Willenbrock, M., Weber, S., Lehmann, T., Schmidt-Arras, D., Schwanbeck, R., Saftig, P., et al. (2012). Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cellular and Molecular Life Sciences, 69(17), 2919-2932. https://doi.org/10.1007/s00018-012-0960-2
Prox, J., Willenbrock, M., Weber, S., Lehmann, T., Schmidt-Arras, D., Schwanbeck, R., Saftig, P., and Schwake, M. (2012). Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cellular and Molecular Life Sciences 69, 2919-2932.
Prox, J., et al., 2012. Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cellular and Molecular Life Sciences, 69(17), p 2919-2932.
J. Prox, et al., “Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10”, Cellular and Molecular Life Sciences, vol. 69, 2012, pp. 2919-2932.
Prox, J., Willenbrock, M., Weber, S., Lehmann, T., Schmidt-Arras, D., Schwanbeck, R., Saftig, P., Schwake, M.: Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10. Cellular and Molecular Life Sciences. 69, 2919-2932 (2012).
Prox, Johannes, Willenbrock, Michael, Weber, Silvio, Lehmann, Tobias, Schmidt-Arras, Dirk, Schwanbeck, Ralf, Saftig, Paul, and Schwake, Michael. “Tetraspanin15 regulates cellular trafficking and activity of the ectodomain sheddase ADAM10”. Cellular and Molecular Life Sciences 69.17 (2012): 2919-2932.
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