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The essential player in adipogenesis GRP78 is a novel KCTD15 interactor
Giovanni Smaldone1, Luciano Pirone2, Angela Capolupo3
1IRCCS SDN, Naples, Italy.
International Journal of Biological Macromolecules
|April 18, 2018
Summary
Potassium channel tetramerization domain 15 (KCTD15) is linked to obesity. This study reveals KCTD15 interacts with GRP78, a protein crucial for adipogenesis, suggesting a conserved mechanism for obesity control.
Area of Science:
- Biochemistry
- Molecular Biology
- Cell Biology
Background:
- KCTD15 (Potassium Channel Tetramerization Domain 15) is implicated in physiological and pathological processes.
- Evidence links KCTD15 to human obesity and its Drosophila homolog to food intake, but its molecular mechanism remains unclear.
Purpose of the Study:
- To elucidate the molecular mechanism of KCTD15 in obesity-related processes.
- To identify KCTD15 interacting partners and understand its role in adipogenesis.
Main Methods:
- Biophysical characterization of recombinant KCTD15.
- Functional proteomic analysis in 3T3-L1 cells to identify KCTD15 interactors.
Main Results:
- KCTD15 exhibits a stable, folded pentameric structure, with the C-terminal domain stabilizing the N-terminal BTB domain.
- GRP78 was identified as a KCTD15 binding partner throughout adipogenesis.
- GRP78 actively stabilizes KCTD15, and this interaction is evolutionarily conserved in Drosophila.
Conclusions:
- The KCTD15-GRP78 complex plays a conserved role in adipogenesis.
- KCTD15, through its interaction with GRP78, represents a potential therapeutic target for obesity management.
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