An endocytic pathway as a target of tubby for regulation of fat storage.

Abstract:

:The tubby loci provide a unique opportunity to study adult-onset obesity. Mutation in either mammalian tubby or its homologue in Caenorhabditis elegans, tub-1, results in increased fat storage. Previously, we have shown that TUB-1 interacts with a new Rab GTPase-activating protein, RBG-3, for the regulation of fat storage. To understand further the molecular mechanism of TUB-1, we identified the Rab GTPase downstream of RBG-3. We found that RBG-3 preferentially stimulates the intrinsic GTPase activity of RAB-7 in both human and C. elegans. Importantly, either mutation or RNA interference knockdown in rab-7 reduces stored fat in wild type and tub-1 mutants. In addition, the small GTPase rab-5 and genes that regulate Rab membrane localization and nucleotide recycling are required for the regulation of fat storage, thereby defining a role for endocytic recycling in this process. We propose that TUB-1 controls receptor or sensory molecule degradation in neurons by regulating a RAB-7-mediated endocytic pathway.

journal_name

EMBO Rep

journal_title

EMBO reports

authors

Mukhopadhyay A,Pan X,Lambright DG,Tissenbaum HA

doi

10.1038/sj.embor.7401055

subject

Has Abstract

pub_date

2007-10-01 00:00:00

pages

931-8

issue

10

eissn

1469-221X

issn

1469-3178

pii

7401055

journal_volume

8

pub_type

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