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. 2019 Aug 5;17:90. doi: 10.1186/s12964-019-0405-8

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© The Author(s). 2019

Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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Fig. 6 — Model. TNF-R1 is palmitoylated in the ER (PAT_x) or Golgi (PAT_y) and transported to caveolae in the plasma membrane. After TNF binding, TNF-R1 is either de-palmitoylated by APT2, resulting in translocation to another lipid raft compartment, complex I formation and signaling for NF-κB activation. Alternatively, TNF-R1 may translocate out of caveolae and TNF-receptosomes are formed by clathrin dependent internalization. This allows complex II/DISC formation by intracellular maturation. In case of APT2 depletion/inhibition, activated TNF-R1 induces nSMase dependent ceramide production in caveolae which triggers cell death