COPI-mediated retrieval of SCAP is critical for regulating lipogenesis under basal and sterol-deficient conditions

Retrograde trafficking from the Golgi apparatus to endoplasmic reticulum (ER) via COPI-coated vesicles has been implicated in lipid homeostasis. Here we found that a block in COPI-dependent retrograde trafficking promoted processing and nuclear translocation of SREBPs (sterol regulatory element bind...

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Veröffentlicht in:Journal of cell science 2015-01
Hauptverfasser: Takashima, Kouhei, Saitoh, Akina, Funabashi, Teruki, Hirose, Shohei, Yagi, Chikako, Nozaki, Shohei, Sato, Ryuichiro, Shin, Hye-Won, Nakayama, Kazuhisa
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Sprache:eng
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Zusammenfassung:Retrograde trafficking from the Golgi apparatus to endoplasmic reticulum (ER) via COPI-coated vesicles has been implicated in lipid homeostasis. Here we found that a block in COPI-dependent retrograde trafficking promoted processing and nuclear translocation of SREBPs (sterol regulatory element binding proteins) and upregulated expression of downstream genes involved in lipid biosynthesis. This elevation in SREBP processing/activation was not caused by mislocalization of S1P or S2P, two Golgi-resident endoproteases involved in SREBP processing, but instead by increased Golgi residence of SREBPs, leading to their increased susceptibility to processing by the endoproteases. Analyses using a processing-defective SREBP mutant suggested that a fraction of SREBP molecules undergo basal cycling between the ER and Golgi in complex with SCAP (SREBP cleavage-activating protein). Furthermore, we showed that SCAP alone is retrieved back from the Golgi to the ER after processing of SREBP under sterol-deficient conditions. Thus, our observations indicate that COPI-mediated retrograde trafficking is critical for preventing unnecessary SREBP activation through retrieval of the SCAP–SREBP complex that basally escapes from the sterol-regulated ER retention machinery, as well as for reuse of SCAP.
ISSN:0021-9533
1477-9137
DOI:10.1242/jcs.164137