Calreticulin facilitates the cell surface expression of ABCG5/G8
Calreticulin facilitates the cell surface expression of ABCG5/G8
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DOI：
10.1016/j.bbrc.2006.06.032
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发表时间：
2006-08-18
影响因子：
3.1
通讯作者：
Kai, Hirofumi
中科院分区：
文献类型：
--
作者：
Okiyoneda, Tsukasa;Kono, Taijun;Kai, Hirofumi
ATP结合盒（ABC）G5（G5）和ABCG 8（G8）异二聚化并作为促进中性固醇的胆汁排泄的固醇转运体起作用。G5和G8都与内质网（ER）中的凝集素样伴侣钙连接蛋白（CNX）相互作用，但这种相互作用的意义尚不清楚。在这里，我们表明不仅CNX，而且其同源物钙网蛋白（CRT）也参与G5/G8固醇转运蛋白的生物合成。CNX和CRT都与G5和G8的未成熟形式相互作用，并通过抑制它们的降解来刺激它们的生产性折叠。有趣的是，CRT主要增强成熟G5/G8的细胞表面表达，而CNX没有类似的效果。N-聚糖加工的抑制剂表明，G5和G8的质量控制可能在ER中受到差异调节。这些发现阐明了CNX和CRT在G5/G8固醇转运蛋白的生物合成和质量控制中的作用。(c)2006年爱思唯尔公司All rights reserved.
ATP-binding cassette (ABC) G5 (G5) and ABCG8 (G8) heterodimerize and function as sterol transporter that promote biliary excretion of neutral sterols. Both G5 and G8 interact with a lectin-like chaperone, calnexin (CNX), in the endoplasmic reticulum (ER) but the significance of this interaction remains unclear. Here, we show that not only CNX, but also its homologue calreticulin (CRT), is involved in the biosynthesis of G5/G8 sterol transporter. Both CNX and CRT interacted with immature forms of G5 and G8, and stimulated their productive folding by inhibiting their degradation. Interestingly, CRT predominantly enhanced the cell surface expression of mature G5/G8 whereas CNX did not have a similar effect. Inhibitors of N-glycan processing indicated that quality control of G5 and G8 might be differentially regulated in the ER. These findings clarify the role of CNX and CRT in the biosynthesis and quality control of G5/G8 sterol transporter. (c) 2006 Elsevier Inc. All rights reserved.