TY - JOUR
T1 - Rab18 promotes lipid droplet (LD) growth by tethering the ER to LDs through SNARE and NRZ interactions
AU - Xu, Dijin
AU - Li, Yuqi
AU - Wu, Lizhen
AU - Li, Ying
AU - Zhao, Dongyu
AU - Yu, Jinhai
AU - Huang, Tuozhi
AU - Ferguson, Charles
AU - Parton, Robert G.
AU - Yang, Hongyuan
AU - Li, Peng
N1 - Funding Information:
This work was supported by grants from the National Natural Science Foundation of China (31690103 and 31430040) to P. Li, the National Key R&D Program of China (2016YFA0502002) to P. Li, the National Health and Medical Research Council, Australia (569542, 1045092, and 1037320), to R.G. Parton, and the National Natural Science Foundation of China (31621063) to P. Li. H. Yang is a Senior Research Fellow of the National Health and Medical Research Council, Australia. The authors declare no competing financial interests.
Publisher Copyright:
© 2018 Xu et al.
PY - 2018/3/1
Y1 - 2018/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85042849577&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85042849577&partnerID=8YFLogxK
U2 - 10.1083/jcb.201704184
DO - 10.1083/jcb.201704184
M3 - Article
C2 - 29367353
AN - SCOPUS:85042849577
SN - 0021-9525
VL - 217
SP - 975
EP - 995
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 3
ER -