Calpain-mediated ABCA1 degradation: Post-translational regulation of ABCA1 for HDL biogenesis

详细信息	查看全文 | 推荐本文 |

• 作者：Shinji Yokoyama^a ; ^{syokoyam@med.nagoya-cu.ac.jp} ; Reijiro Arakawa^b ; Cheng-ai Wu^b ; Noriyuki Iwamoto^b ; Rui Lu^a ; Maki Tsujita^b ; Sumiko Abe-Dohmae^b
• 关键词：ABCA1 ; Calpain ; HDL ; Cholesterol ; Atherosclerosis
• 刊名：Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids
• 出版年：2012
• 期刊代码：18_13881981
• 类别：bio
• 出版时间：March, 2012
• 卷：1821
• 期：3
• 页码：547-551
• 文件大小：734 K

摘要

Helical apolipoproteins remove cellular phospholipid and cholesterol to generate nascent HDL and this reaction is the major source of plasma HDL. ABCA1 is mandatory and rate-limiting for this reaction. Besides regulation of the gene expression by transcriptional factors including LXR, AP2 and SREBP, the ABCA1 activity is regulated post-translationally by calpain-mediated proteolytic degradation of ABCA1 protein that occurs in the early endosome after its endocytosis. When the HDL biogenesis reaction is ongoing as helical apolipoproteins interact with ABCA1, ABCA1 becomes resistant to calpain and is recycled to cell surface after endocytosis. Biogenesis of HDL is most likely to take place on cell surface. Clearance rate of ABCA1 by this mechanism is also retarded by various factors that interact with ABCA1, such as 伪1-syntrophin, LXR尾 and calmodulin. Physiological relevance of the retardation by these factors is not entirely clear. Pharmacological inhibition of the calpain-mediated ABCA1 degradation results in the increase of the ABCA1 activity and HDL biogenesis in vitro and in vivo, and potentially suppresses atherogenesis. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).