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PHYSIOLOGICAL FUNCTION OF LIPID DROPLETS AND REGULATION OF INTRACELLULAR LIPID TRAFFICKING

脂滴的生理功能和细胞内脂质运输的调节

基本信息

批准号：
17390051
负责人：
FUJIMOTO Toyoshi
金额：
$ 9.34万
依托单位：
NAGOYA UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2005
资助国家：
日本
起止时间：
2005 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390051/
关键词：
lipid droplets ADRP TIIP47 Rabl8 ApoB proteasome autophagy カベオリンコレステロール

项目摘要

The dynamic properties of lipid droplets have become more apparent by our recent studies. During the period supported by the current grant, we obtained the following results.1. Rabl8 was found to localize to lipid droplets specifically. When Rab18 was overexpressed, ADRP decreased, and close association of lipid droplets and the endoplasmic reticulum became prominent. The same structure also increased upon knockdown of ADRP or by brefeldin A treatment. These results suggested that Rab18 induces the lipid droplet-associated membrane structure (LAM) through dislocation of ADRP.2. In hepatocyte-derived cell lines (Huh7, HepG2), ApoB was found to form a crescent-shaped structure around lipid droplets (ApoB-crescent). The ApoB-crescent increased drastically when proteasome or autophagy was prohibited. Proteasomal subunits were concentrated around lipid droplets, and ApoB recovered in the lipid droplet fraction was highly ubiquitinated. The result suggested that lipid droplets are a platform for ApoB to be processed by proteasome and autophagy.3. TIP47, a member of PAT family proteins, was recruited to lipid droplets when cells were added with fatty acids. The localization of TIP47 to lipid droplets required its N-terminal portion. On the other hand, disruption of the C-terminal portion, which was speculated to form a hydrophobic cleft, induced constitutive localization to lipid droplets.These results further revealed that lipid droplets have a variety of functions in relation to intracellular lipid homeostasis.

脂滴的动力学性质在我们最近的研究中变得更加明显。在本次资助的资助期间，我们取得了以下成果。1.发现Rabl 8特异性定位于脂滴。当Rab 18过表达时，ADRP下降，脂滴和内质网的紧密结合变得突出。同样的结构也增加敲低ADRP或通过布雷菲德菌素A治疗。这些结果表明Rab 18通过ADRP的移位诱导脂滴相关膜结构（LAM）的形成.在肝细胞衍生的细胞系（Huh 7、HepG 2）中，发现ApoB在脂滴周围形成新月形结构（ApoB-新月体）。当蛋白酶体或自噬被禁止时，ApoB-新月体急剧增加。蛋白酶体亚基集中在脂滴周围，脂滴组分中的ApoB被高度泛素化。提示脂滴是ApoB被蛋白酶体加工和自噬的平台. TIP 47是PAT家族蛋白的一员，当细胞加入脂肪酸时，它被募集到脂滴中。TIP 47定位于脂滴需要其N-末端部分。另一方面，C-末端部分的破坏，这被推测为形成一个疏水裂缝，诱导组成性定位到脂滴。这些结果进一步揭示了脂滴具有多种功能，在细胞内脂质稳态。