文章基本信息

标题：Reduced cholesterol and triglycerides in mice with a mutation in Mia2, a liver protein that localizes to ER exit sites
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作者：Jeffrey L. Pitman ; David J. Bonnet ; Linda K. Curtiss 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2011
卷号：52
期号：10
页码：1775-1786
DOI：10.1194/jlr.M017277
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：Through forward genetic screening in the mouse, a recessive mutation ( couch potato , cpto ) has been discovered that dramatically reduces plasma cholesterol levels across all lipoprotein classes. The cpto mutation altered a highly conserved residue in the Src homology domain 3 (SH3) domain of the Mia2 protein. Full-length hepatic Mia2 structurally and functionally resembled the related Mia3 protein. Mia2 localized to endoplasmic reticulum (ER) exit sites, suggesting a role in guiding proteins from the ER to the Golgi. Similarly to the Mia3 protein, Mia2’s cytosolic C terminus interacted directly with COPII proteins Sec23 and Sec24, whereas its lumenal SH3 domain may facilitate interactions with secretory cargo. Fractionation of plasma revealed that Mia2 ^cpto/cpto mice had lower circulating VLDL, LDL, HDL, and triglycerides. Mia2 is thus a novel, hepatic, ER-to-Golgi trafficking protein that regulates cholesterol metabolism.
关键词：endoplasmic reticulum ; lipoprotein ; secretion ; Mia3 ; Tango1 ; Ctage5