C. elegans tubby regulates life span and fat storage by two independent mechanisms
In C. elegans, similar to in mammals, mutations in the tubby homolog, tub-1, promote increased fat deposition. Here, we show that mutation in tub-1 also leads to life span extension dependent on daf-16/FOXO. Interestingly, function of tub-1 in fat storage is independent of daf-16. A yeast two-hybrid screen identified a novel TUB-1 interaction partner (RBG-3); a RabGTPase-activating protein. Both TUB-1 and RBG-3 localize to overlapping neurons. Importantly, RNAi of rbg-3 decreases fat deposition in tub-1 mutants but does not affect life span. We demonstrate that TUB-1 is expressed in ciliated neurons and undergoes both dendritic and ciliary transport. Additionally, tub-1 mutants are chemotaxis defective. Thus, tub-1 may regulate fat storage either by modulating transport, sensing, or responding to signals in ciliated neurons. Taken together, we define a role for tub-1 in regulation of life span and show that tub-1 regulates life span and fat storage by two independent mechanisms.
Keywords: Adipose Tissue/metabolism ; Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics/physiology ; Caenorhabditis elegans Proteins/chemistry/genetics/metabolism ; Chemotaxis ; Cilia/physiology ; Insulin/metabolism ; Insulin-Like Growth Factor I/metabolism ; Lipid Metabolism ; Longevity/genetics/physiology ; Models ; Biological ; Molecular Sequence Data ; Mutation/genetics ; Neurons/cytology/metabolism ; Protein Binding ; Protein Transport ; RNA Interference ; Sequence Alignment ; Transcription Factors/metabolism ; rab GTP-Binding Proteins/chemistry/metabolism
Record created on 2008-07-15, modified on 2016-08-08