title: Derlin-1 and UBXD8 are engaged in dislocation and degradation of lipidated ApoB-100 at lipid droplets.
abstract: 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.
authors.affiliation: Department of Anatomy and Molecular Cell Biology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa, Nagoya 466-8550, Japan.
authors.forename: Michitaka
authors.initials: M
authors.lastname: Suzuki
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Otsuka
authors.forename: Yuki
authors.initials: Y
authors.lastname: Ohsaki
authors.forename: Jinglei
authors.initials: J
authors.lastname: Cheng
authors.forename: Takako
authors.initials: T
authors.lastname: Taniguchi
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hashimoto
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Taniguchi
authors.forename: Toyoshi
authors.initials: T
authors.lastname: Fujimoto
mesh_terms: D000818:Animals; D053299:Apolipoprotein B-100 / Q000378:metabolism*; D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D003593:Cytoplasm / Q000378:metabolism; D060746:Endoplasmic Reticulum-Associated Degradation; D006367:HeLa Cells; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D059748:Proteolysis; D034741:RNA, Small Interfering / Q000235:genetics
chemical_list: D053299:Apolipoprotein B-100; D001798:Blood Proteins; C487709:DERL1 protein, human; C468782:FAF2 protein, human; D008565:Membrane Proteins; D034741:RNA, Small Interfering