C. elegans tubby regulates life span and fat storage by two independent mechanisms

Cell Metab. 2005 Jul;2(1):35-42. doi: 10.1016/j.cmet.2005.06.004.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Amino Acid Sequence
  • Animals
  • Caenorhabditis elegans / genetics
  • Caenorhabditis elegans / physiology*
  • Caenorhabditis elegans Proteins / chemistry
  • Caenorhabditis elegans Proteins / genetics
  • Caenorhabditis elegans Proteins / metabolism*
  • Chemotaxis
  • Cilia / physiology
  • Forkhead Transcription Factors
  • Insulin / metabolism
  • Insulin-Like Growth Factor I / metabolism
  • Lipid Metabolism*
  • Longevity / genetics
  • Longevity / physiology*
  • Models, Biological
  • Molecular Sequence Data
  • Mutation / genetics
  • Neurons / cytology
  • Neurons / metabolism
  • Protein Binding
  • Protein Transport
  • RNA Interference
  • Sequence Alignment
  • Transcription Factors / metabolism
  • rab GTP-Binding Proteins / chemistry
  • rab GTP-Binding Proteins / metabolism

Substances

  • Caenorhabditis elegans Proteins
  • Forkhead Transcription Factors
  • Insulin
  • Transcription Factors
  • daf-16 protein, C elegans
  • tub-1 protein, C elegans
  • Insulin-Like Growth Factor I
  • rab GTP-Binding Proteins