The essential player in adipogenesis GRP78 is a novel KCTD15 interactor.

KCTD15 is a member of the K+ Channel Tetramerization Domain family, implicated in crucial physio-pathological processes. Recent evidences suggest that KCTD15 is an obesity-linked protein in humans and its Drosophila homologue is involved in food uptake. KCTD15 molecular mechanism in these processes is still unknown. To fill this gap, KCTD15 was biophysically characterized showing a folded, pentameric region endowed with a remarkable thermal stability. Notably, the C-terminal domain significantly contributes to the stabilization of the BTB N-terminal domain. The availability of large amount of stable recombinant protein also made possible a functional proteomic approach in 3T3-L1 cells to search for novel KCTD15 interactors. These investigations led to the discovery that GRP78 is a KCTD15 partner in all the adipogenesis phases. Our data clearly prove the physical interaction of the two proteins and also indicate that GRP78 plays an active role in the stabilization of KCTD15. Furthermore, the presence in Drosophila of a GRP78 homologue corroborates the physiological role played by the complex KCTD15-GRP78 in the adipogenesis process and indicates that it is evolutionarily conserved. Present results also suggest that KCTD15 may be a new target for obesity control.