Rab30 regulates lipid homeostasis in the hepatocyte during fasting
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1003498 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR25573246_1.fastq.gz | Fastqsanger.gz | |||
| SRR25573246_2.fastq.gz | Fastqsanger.gz | |||
| SRR25573247_1.fastq.gz | Fastqsanger.gz | |||
| SRR25573247_2.fastq.gz | Fastqsanger.gz | |||
| SRR25573248_1.fastq.gz | Fastqsanger.gz |
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Project description:In order to facilitate inter-tissue communication and exchange of proteins, lipoproteins, and metabolites with the circulation, hepatocytes have an intricate and efficient intracellular trafficking system regulated by small Rab GTPases. Rab30, a putative Golgi-localized Rab GTPase, is induced in the mouse liver by fasting and its expression is further amplified in liver-specific carnitine palmitoyltransferase 2 knockout mice (Cpt2L-/-) that lack the ability to oxidize fatty acids in a Pparα-dependent manner. Live-cell super-resolution imaging and biochemical in vivo proximity labeling demonstrated that Rab30-marked vesicles are highly dynamic and interact with proteins throughout the secretory pathway. Rab30 whole-body, liver-specific, and Rab30;Cpt2 liver-specific double knockout (DKO) mice are viable and display intact Golgi ultrastructure. However, the loss of Rab30 in Rab30;Cpt2 DKO mice suppresses serum dyslipidemia observed in Cpt2L-/- single knockout mice. Corresponding with decreased serum triglyceride and cholesterol levels, Rab30;Cpt2 DKO mice exhibit decreased circulating but not hepatic ApoA4 protein, indicative of a trafficking defect. Together, these data suggest a role for Rab30 in the selective sorting of lipoproteins to influence hepatocyte and circulating triglyceride levels particularly during times of excessive lipid burden.
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