C. elegans tubby regulates life span and fat storage by two independent mechanisms
Program in Gene Function and Expression; Program in Molecular Medicine
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.
DOI of Published Version
Cell Metab. 2005 Jul;2(1):35-42. Link to article on publisher's site
Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA. (2005). C. elegans tubby regulates life span and fat storage by two independent mechanisms. Program in Gene Function and Expression Publications. https://doi.org/10.1016/j.cmet.2005.06.004. Retrieved from https://escholarship.umassmed.edu/pgfe_pp/21