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

Takashima, Kouhei, Saitoh, Akina, Funabashi, Teruki, Hirose, Shohei, Yagi, Chikako, Nozaki, Shohei, Sato, Ryuichiro, Shin, Hye-Won, Nakayama, Kazuhisa·2015·Journal of Cell Science
DOI 10.1242/jcs.164137
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Abstract

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.

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Research works printed but not linked: 33

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Metadata

Authors
Takashima, K., Saitoh, A., Funabashi, T., Hirose, S., Yagi, C., Nozaki, S., Sato, R., Shin, H.-W., & Nakayama, K.
Venue
Journal of Cell Science
Publisher
The Company of Biologists
Published
2015-01-01
ISSN
  • 1477-9137
  • 0021-9533
DOI
10.1242/jcs.164137
Cited by
15
References
0
Language
en

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