Rab18 regulates lipolysis via Arf/GBF1 and adipose triglyceride lipase
Autor: | John F. Presley, Selma Yilmaz Dejgaard |
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Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Lipolysis Recombinant Fusion Proteins Green Fluorescent Proteins Biophysics Models Biological Biochemistry 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Lipid droplet Guanine Nucleotide Exchange Factors Humans Small GTPase Molecular Biology Brefeldin A ADP-Ribosylation Factors Autophagy Lipase Lipid Droplets Cell Biology Cell biology Cytosol 030104 developmental biology chemistry rab GTP-Binding Proteins 030220 oncology & carcinogenesis Adipose triglyceride lipase lipids (amino acids peptides and proteins) Guanosine Triphosphate RAB18 HeLa Cells Protein Binding |
Zdroj: | Biochemical and Biophysical Research Communications. 520:526-531 |
ISSN: | 0006-291X |
Popis: | Rab18 is a small GTPase associated with lipid droplets and other membranes. While it likely has multiple functions on lipid droplets, one proposed function is regulation of lipolysis. Previous work has concentrated on regulation of autophagy; however, in this study, we provide evidence that Rab18 plays a role upstream of the cytosolic lipolytic enzyme adipose triglyceride lipase (ATGL) and that recruitment of ATGL by Rab18 is mediated by elements of the Arf/GBF1 machinery. We find that Arf4-GFP is accumulated on the subset of lipid droplets associated with Rab18, and that this association is lost within 5 min upon treatment with 5 μg/ml of the drug brefeldin A, which targets GBF1 and other Sec7-domain containing Arf exchange factors. ATGL-GFP is also recruited to lipid droplets, but is lost more slowly after treatment with 5 μg/ml brefeldin A, with significant loss from lipid droplets after 1 h treatment, and almost complete loss from lipid droplets 4 h after brefeldin A treatment. Upon overexpression of the dominant negative GDP-locked cerulean-Rab18-S22 N, GFP-ATGL and Arf4 are lost from the surface of lipid droplets similarly to BFA treatment. This study establishes, for the first time, an essential role for Rab18 in recruiting ATGL to lipid droplets. |
Databáze: | OpenAIRE |
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