Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets.
Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets.
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DOI：
10.1091/mbc.e11-11-0950
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发表时间：
2012-03
影响因子：
3.3
通讯作者：
Fujimoto T
中科院分区：
文献类型：
--
作者：
Suzuki M;Otsuka T;Ohsaki Y;Cheng J;Taniguchi T;Hashimoto H;Taniguchi H;Fujimoto T
脂化后的载脂蛋白B-100从ER腔移位到脂滴的细胞质表面，进行蛋白酶体降解。脂滴中的UBXD 8和ER膜中的Derlin-1相互作用，并与ApoB相互作用，分别参与前和后位错步骤。载脂蛋白B-100（ApoB）是极低密度脂蛋白的主要成分。脂化不良的新生ApoB从Sec 61易位子中提取并被蛋白酶体降解。在内质网（ER）腔中脂化的ApoB也受到蛋白酶体降解，但它在哪里以及如何移位到细胞质仍然未知。在本研究中，我们证明了脂化后的载脂蛋白B被移位到脂滴（LDs）的细胞质表面，并在Huh 7细胞中积累为泛素化的载脂蛋白B。UBXD 8的耗尽，其几乎局限于该细胞类型中的LD，减少了p97向LD的募集，并导致LD表面上的泛素化ApoB和ER腔中的脂化ApoB两者的增加。相反，Derlin-1功能的废除诱导ER腔中脂化ApoB的积累，但不增加LD表面上的泛素化ApoB。UBXD 8和Derlin-1相互结合并与脂化ApoB结合，并显示出LD周围的共定位。这些结果表明，脂化后的载脂蛋白B从ER腔移位到LD表面的蛋白酶体降解和Derlin-1和UBXD 8从事的predislocation和postdislocation步骤，分别。
Apolipoprotein B-100 after lipidation is dislocated from the ER lumen to the cytoplasmic surface of lipid droplets for proteasomal degradation. UBXD8 in lipid droplets and Derlin-1 in the ER membrane interact with each other and with ApoB and are engaged in the pre- and postdislocation steps, respectively. Apolipoprotein B-100 (ApoB) is the principal component of very low density lipoprotein. Poorly lipidated nascent ApoB is extracted from the Sec61 translocon and degraded by proteasomes. ApoB lipidated in the endoplasmic reticulum (ER) lumen is also subjected to proteasomal degradation, but where and how it dislocates to the cytoplasm remain unknown. In the present study, we demonstrate that ApoB after lipidation is dislocated to the cytoplasmic surface of lipid droplets (LDs) and accumulates as ubiquitinated ApoB in Huh7 cells. Depletion of UBXD8, which is almost confined to LDs in this cell type, decreases recruitment of p97 to LDs and causes an increase of both ubiquitinated ApoB on the LD surface and lipidated ApoB in the ER lumen. In contrast, abrogation of Derlin-1 function induces an accumulation of lipidated ApoB in the ER lumen but does not increase ubiquitinated ApoB on the LD surface. UBXD8 and Derlin-1 bind with each other and with lipidated ApoB and show colocalization around LDs. These results indicate that ApoB after lipidation is dislocated from the ER lumen to the LD surface for proteasomal degradation and that Derlin-1 and UBXD8 are engaged in the predislocation and postdislocation steps, respectively.