Tubby protein homolog

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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.

MeSH Terms

  • Adipose Tissue
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans
  • Caenorhabditis elegans Proteins
  • Chemotaxis
  • Cilia
  • Forkhead Transcription Factors
  • 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