期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 27, 期 10, 页码 3716-3731出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.00931-06
关键词
-
资金
- NHLBI NIH HHS [T32 HL007675, T32 HL 007675] Funding Source: Medline
- NIDDK NIH HHS [R24 DK 071030, R21 DK 075887-01, R24 DK071030, R21 DK075887, R01 DK055758, T32 DK007513, T32 DK 007513, R01 DK 55758] Funding Source: Medline
- NIGMS NIH HHS [T32 GM007288, T32 GM 07288] Funding Source: Medline
Adiponectin is a secretory protein abundantly secreted from adipocytes. It assembles into a number of different higher-order complexes. Adipocytes maintain tight control over circulating plasma levels, suggesting the existence of a complex, highly regulated biosynthetic pathway. However, the critical mediators of adiponectin maturation within the secretory pathway have not been elucidated. Previously, we found that a significant portion of de novo-synthesized adiponectin is not secreted and retained in adipocytes. Here, we show that there is an abundant pool of properly folded adiponectin in the secretory pathway that is retained through thiol-mediated retention, as judged by the release of adiponectin in response to treatment of adipocytes with reducing agents. Adiponectin is covalently bound to the ER chaperone ERp44. An adiponectin mutant lacking cysteine 39 fails to stably interact with ERp44, demonstrating that this residue is the primary site mediating the covalent interaction. Another ER chaperone, Ero1-L alpha, plays a critical role in the release of adiponectin from ERp44. Levels of both of these proteins are highly regulated in adipocytes and are influenced by the metabolic state of the cell. While less critical for the secretion of trimers, these chaperones play a major role in the assembly of higher-order adiponectin complexes. Our data highlight the importance of posttranslational events controlling adiponectin levels and the release of adiponectin from adipocytes. One mechanism for increasing circulating levels of specific adiponectin complexes by peroxisome proliferator-activated receptor gamma agonists may be selective upregulation of rate-limiting chaperones.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据