Abstract | OBJECTIVE: METHODS: We employed co-immunoprecipitation and immunofluorescence methods to determine whether seipin can interact with AGPAT2 and the consequences of this in developing adipocytes. Atomic force microscopy was used to determine whether these interactions involved direct association of the proteins and to define the molecular architecture of these complexes. RESULTS: Our data reveal that seipin can bind AGPAT2 during adipogenesis and that stabilizing this interaction during adipogenesis can increase the nuclear accumulation of PPARĪ³. Both AGPAT2 and lipin 1 can directly associate with seipin dodecamers, and a single seipin complex can simultaneously bind both AGPAT2 and lipin with a defined orientation. CONCLUSIONS: Our study provides the first direct molecular link between seipin and AGPAT2, two proteins whose disruption causes CGL. Moreover, it provides the first example of an interaction between seipin and another protein that causally influences a key aspect of adipogenesis. Together our data suggest that the critical role of seipin in adipogenesis may involve its capacity to juxtapose important regulators of this process in a multi- protein complex.
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Authors | Md Mesbah Uddin Talukder, M F Michelle Sim, Stephen O'Rahilly, J Michael Edwardson, Justin J Rochford |
Journal | Molecular metabolism
(Mol Metab)
Vol. 4
Issue 3
Pg. 199-209
(Mar 2015)
ISSN: 2212-8778 [Print] Germany |
PMID | 25737955
(Publication Type: Journal Article)
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