Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions

Dijin Xu, Yuqi Li, Lizhen Wu, Ying Li, Dongyu Zhao, Jinhai Yu, Tuozhi Huang, Charles Ferguson, Robert G. Parton, Hongyuan Yang, Peng Li

Research output: Contribution to journalArticlepeer-review

108 Scopus citations


Lipid incorporation from endoplasmic reticulum (ER) to lipid droplet (LD) is important in controlling LD growth and intracellular lipid homeostasis. However, the molecular link mediating ER and LD cross talk remains elusive. Here, we identified Rab18 as an important Rab guanosine triphosphatase in controlling LD growth and maturation. Rab18 deficiency resulted in a drastically reduced number of mature LDs and decreased lipid storage, and was accompanied by increased ER stress. Rab3GAP1/2, the GEF of Rab18, promoted LD growth by activating and targeting Rab18 to LDs. LD-associated Rab18 bound specifically to the ER-associated NAG-RINT1-ZW10 (NRZ) tethering complex and their associated SNA REs (Syntaxin18, Use1, BNIP1), resulting in the recruitment of ER to LD and the formation of direct ER-LD contact. Cells with defects in the NRZ/SNA RE complex function showed reduced LD growth and lipid storage. Overall, our data reveal that the Rab18-NRZ-SNA RE complex is critical protein machinery for tethering ER-LD and establishing ER-LD contact to promote LD growth.

Original languageEnglish (US)
Pages (from-to)975-995
Number of pages21
JournalJournal of Cell Biology
Issue number3
StatePublished - Mar 1 2018
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology


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