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

Authors: Mukhopadhyay A; Deplancke B; Walhout AJ; Tissenbaum HA

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.

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
Journal: Cell metabolism
Volume: 2
Issue: 1
Pages: 35-42
Date: Aug. 2, 2005
PMID: 16054097
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Citation:

Mukhopadhyay A, Deplancke B, Walhout AJ, Tissenbaum HA (2005) C. elegans tubby regulates life span and fat storage by two independent mechanisms. Cell metabolism 2: 35-42.


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