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First published online 12 August 2008
doi: 10.1242/jcs.026153

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Multiple functions encoded by the N-terminal PAT domain of adipophilin

¹ Department of Pathology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
² Department of Obstetrics and Gynecology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
³ Graduate Program in Molecular Biology, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
⁴ Graduate Program in Reproductive Sciences, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA
⁵ Graduate Program in Cell Biology, Stem Cells and Development, University of Colorado Denver, Anschutz Medical Campus, Aurora, CO 80045, USA

^* Author for correspondence (e-mail: jim.mcmanaman{at}uchsc.edu)

Accepted 16 June 2008

Adipophilin (ADPH), a member of the perilipin family of cytoplasmic lipid droplet (CLD)-binding proteins, is crucially dependent on triglyceride synthesis for stability. We have used cell lines expressing full-length or N-terminally modified forms of ADPH to investigate the role of the N-terminus in regulating ADPH stability and interactions with CLD. Full-length ADPH was unstable and could not be detected on CLDs unless cultures were incubated with oleic acid (OA) to stimulate triglyceride synthesis, or were treated with MG132 to block proteasomal degradation. By contrast, ADPH lacking amino acids 1-89 ( 2,3 ADPH), or N-terminally GFP-tagged full-length ADPH, was stable in the absence of OA or MG132, as was the closely related protein TIP47. However, none of these proteins localized to CLDs unless OA was added to the culture medium. Furthermore, immunofluorescence analysis showed that TIP47 localization to CLDs was prevented by full-length ADPH, but not by 2,3 ADPH. These results suggest that the N-terminal region of ADPH mediates proteasomal degradation and access of TIP47 to the CLD surface and possibly contributes to CLD stability. Chimeras of ADPH and TIP47, generated by swapping their N- and C-terminal halves, showed that these properties are specific to ADPH.

Key words: Adipophilin (ADPH; ADFP), TIP47 (M6PRBP1), Lipid droplets, Proteasome, Domain

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