Cul3 neddylation is crucial for gradual lipid droplet formation during adipogenesis

Biochimica Et Biophysica Acta. Molecular Cell Research
Dawadschargal DubielMichael Naumann

Abstract

Cullin 3 (Cul3) belongs to the family of cullins (Cul1-7) providing the scaffold for cullin-RING ubiquitin (Ub) ligases (CRLs), which are activated by neddylation and represent essential E3 ligases of the Ub proteasome system. During adipogenic differentiation neddylated Cul3 accumulates in LiSa-2 preadipocytes. Downregulation of Cul3 and inhibition of neddylation by MLN4924 blocks the formation of lipid droplets (LDs), the lipid storage organelles and markers of adipogenesis. Neddylation of Cul3 coincides with an increase of Rab18, a GTPase associated with LDs. Immunoprecipitation and confocal fluorescence microscopy revealed physical association of Cul3 and Rab18 at the membrane of LDs. RhoA, a suppressor of adipogenesis decreased during differentiation. Our results in LiSa-2 cells, but also mouse embryonic fibroblasts revealed a connection between Cul3, Rab18 and RhoA. Downregulation of Cul3 led to a marked increase in RhoA protein expression after 6days of LiSa-2 cell differentiation, suggesting that Cul3 is involved in the regulation of RhoA stability.

Citations

Jun 20, 2019·American Journal of Physiology. Cell Physiology·Deng-Fu Guo, Kamal Rahmouni
Feb 23, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Abhishek SinhaElah Pick
Jan 17, 2020·Proceedings of the National Academy of Sciences of the United States of America·Xueying ZhangJiyan Zhang
Oct 8, 2020·The FEBS Journal·Tao Zou, Jiyan Zhang
Dec 19, 2017·Trends in Biochemical Sciences·Wolfgang DubielMichael Naumann
Oct 4, 2020·Biochimica Et Biophysica Acta. Molecular and Cell Biology of Lipids·Vitor TeixeiraVítor Costa
Jun 8, 2021·Nucleic Acids Research·Katharina SchmitzChristoph Peter

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