SPPL2a and SPPL2b promote intramembrane proteolysis of TNFα in activated dendritic cells to trigger
Author: ["Elena Friedmann","Ehud Hauben","Kerstin Maylandt","Simone Schleeger","Sarah Vreugde","Stefan F. Lichtenthaler","Peer-Hendrik Kuhn","Daniela Stauffer","Giorgio Rovelli","Bruno Martoglio"]
Publication: Nature Cell Biology
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Abstract
Homologues of signal peptide peptidase (SPPLs) are putative aspartic proteases that may catalyse regulated intramembrane proteolysis of type II membrane-anchored signalling factors. Here, we show that four human SPPLs are each sorted to a different compartment of the secretory pathway. We demonstrate that SPPL2a and SPPL2b, which are sorted to endosomes and the plasma membrane, respectively, are functional proteases that catalyse intramembrane cleavage of tumour necrosis factor alpha (TNFα). The two proteases promoted the release of the TNFα intracellular domain, which in turn triggers expression of the pro-inflammatory cytokine interleukin-12 by activated human dendritic cells. Our study reveals a critical function for SPPL2a and SPPL2b in the regulation of innate and adaptive immunity.
Cite this article
Friedmann, E., Hauben, E., Maylandt, K. et al. SPPL2a and SPPL2b promote intramembrane proteolysis of TNFα in activated dendritic cells to trigger IL-12 production. Nat Cell Biol 8, 843–848 (2006). https://doi.org/10.1038/ncb1440
