C. elegans tubby regulates life span and fat storage by two independent mechanisms
Program in Gene Function and Expression; Program in Molecular Medicine
Medical Subject Headings
Adipose Tissue; Amino Acid Sequence; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Chemotaxis; Cilia; Insulin; Insulin-Like Growth Factor I; *Lipid Metabolism; Longevity; Models, Biological; Molecular Sequence Data; Mutation; Neurons; Protein Binding; Protein Transport; RNA Interference; Sequence Alignment; Transcription Factors; rab GTP-Binding Proteins
Genetics and Genomics
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.
Rights and Permissions
Citation: Cell Metab. 2005 Jul;2(1):35-42. Link to article on publisher's site