The transport protein particle (TRAPP) was initially identified as a vesicle tethering factor in yeast and as a guanine nucleotide exchange factor (GEF) for Ypt1/Rab1. In mammals, structures and functions of various TRAPP complexes are beginning to be understood. We found that mammalian TRAPPII was a GEF for both Rab18 and Rab1. Inactivation of TRAPPII‐specific subunits by various methods including siRNA depletion and CRISPR–Cas9‐mediated deletion reduced lipolysis and resulted in aberrantly large lipid droplets. Recruitment of Rab18 onto lipid droplet (LD) surface was defective in TRAPPII‐deleted cells, but the localization of Rab1 on Golgi was not affected. COPI regulates LD homeostasis. We found that the previously documented interaction between TRAPPII and COPI was also required for the recruitment of Rab18 to the LD. We hypothesize that the interaction between COPI and TRAPPII helps bring TRAPPII onto LD surface, and TRAPPII, in turn, activates Rab18 and recruits it on the LD surface to facilitate its functions in LD homeostasis.
Mammalian TRAPPII serves as a GEF for Rab18 and, together with COPI, regulates its recruitment onto the lipid droplet surface, thereby controlling lipid homeostasis.
Mammalian TRAPPII serves as a GEF for Rab18.
COPI–TRAPPII recruits Rab18 onto the surface of small lipid droplets.
Defective TRAPPII function results in defective lipolysis and aberrantly large lipid droplets.
- Received May 25, 2016.
- Revision received November 11, 2016.
- Accepted November 16, 2016.
- © 2016 The Authors
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