A RasGAP, DAB2IP, regulates lipid droplet homeostasis by serving as GAP toward RAB40C

Xiaomin Luo, Chunman Li, Ran Tan, Xiaohui Xu, William K.K. Wu, Ayano Satoh, Tuanlao Wang, Sidney Yu

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)

Abstract

Lipid droplet (LD) homeostasis involves activities of various RAB small GTPases. Recently, we found RAB40C was one of the RAB proteins regulating LD homeostasis. RAB40C contains a unique SOCS domain that is required for clustering of LDs. However, its precise functional role in LD homeostasis and mechanism of regulation remain largely unknown. In this study, we observed over-accumulation of LDs in cells with RAB40C deleted by Crispr-Cas9 editing. RAB40C appeared to reduce LD accumulation after long term incubation of cells with oleic acid (24 hours). Unexpectedly, we found that Ras GTPase activating protein (GAP), DAB2IP, bound to RAB40C mainly via its GAP domain and could serve as RAB40C GAP. Studies involving overexpression of DAB2IP and its GAP defective mutant and siRNA depletion of DAB2IP all confirmed that DAB2IP negatively regulated the effect of RAB40C on LD homeostasis. These results provide a novel perspective on the regulation of RAB40C and implicate various signalling pathways regulated by DAB2IP, which may play a role in LD homeostasis via RAB40C.

Original languageEnglish
Pages (from-to)85415-85427
Number of pages13
JournalOncotarget
Volume8
Issue number49
DOIs
Publication statusPublished - Oct 17 2017

Keywords

  • DAB2IP
  • GTPase activating protein
  • Lipid droplets
  • RAB40C

ASJC Scopus subject areas

  • Oncology

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