Figure 5.

The effectors of PKD at the TGN. (A) PKD is recruited to the TGN by DAG and ARF1. Activated PKD phosphorylates to activate PI4KIIIß thus promoting the production of PI4P in the outer leaflet of the TGN. (B) PI4P recruits a number of proteins to the TGN membrane, including OSBP and CERT. (C) OSBP and CERT regulate the sphingomyelin and sterol levels in the TGN and this we suggest is required for separating the PI4P containing domain from the SM and sterol rich domain. CERT dependent ceramide transport to the TGN, we suggest is required to generate and concentrate DAG at the TGN. (D) This DAG in turn recruits more PKD to generate more DAG. PKD then phosphorylates OSBP and CERT to release them from the TGN. (E) ARF1 mediated activation of PLD1 generates PA from the PC pool, which eventually is converted to LPA by the action of PLA2. The accumulation of these different modified lipids leads to fission of TGN to cell surface transport carriers. (F) DAG is consumed thus dissociating PKD from the membrane thus resetting the TGN to generate another round of transport carriers in a cargo-dependent manner.