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Binding of liposomes composed of phosphatidylcholine to scavenger receptor class B type 1 and its modulation by phosphatidic acid in HEK293T cells
Biochimica et Biophysica Acta (BBA) - Molecular Cell Research ( IF 4.6 ) Pub Date : 2021-04-14 , DOI: 10.1016/j.bbamcr.2021.119043
Narumi Koide 1 , Kazuyo Fujita 2 , Shun'ichi Kuroda 3 , Shuji Hinuma 3
Affiliation  

In this study, we developed a method to analyze liposomal binding to a cell membrane receptor using fluorescence-labeled liposomes and demonstrated that scavenger class B type 1 (SR-B1) plays a crucial role in binding of liposomes containing phosphatidylcholine (PC) to HEK293T cell membrane and phosphatidic acid (PA) can modulate it. Site-directed mutagenesis of SR-B1 revealed that S112F and T175A mutations in its ectodomain abrogated binding and endocytosis of PC liposomes in HEK293T cells. K151A and K156A mutations attenuated their binding and endocytosis too. Although the effects of mutations on binding and endocytosis were similar between PC liposomes and PC/PA and PA liposomes, SR-B1 dependency appeared to be PC > PC/PA > PA liposomes. Our data indicate that (i) nanoparticles including high-density lipoprotein (HDL), silica, and liposomes bind to a common or close site of SR-B1, and (ii) PC/PA and PA liposomes bind not only to SR-B1 but also other receptor(s) in HEK293T cells. In addition, PC/PA liposomes induced lipid droplet (LD) formation in HEK293T cells more than PC liposomes. Treatment of HEK293T cells with SR-B1 siRNA suppressed PC/PA liposome-induced LD formation. Taken together, our results demonstrate that SR-B1 plays an essential role in binding PC-containing liposomes and the subsequent induction of cellular responses, while PA can modulate them.



中文翻译:

HEK293T细胞中磷脂酰胆碱脂质体与B类清道夫受体1型的结合及其对磷脂酸的调节

在这项研究中,我们开发了一种使用荧光标记的脂质体分析脂质体与细胞膜受体结合的方法,并证明 B 类清道夫 (SR-B1) 在含有磷脂酰胆碱 (PC) 的脂质体与 HEK293T 的结合中起关键作用细胞膜和磷脂酸 (PA) 可以调节它。SR-B1 的定点诱变显示其胞外域中的 S112F 和 T175A 突变取消了 HEK293T 细胞中 PC 脂质体的结合和内吞作用。K151A 和 K156A 突变也减弱了它们的结合和内吞作用。尽管突变对结合和内吞作用的影响在 PC 脂质体与 PC/PA 和 PA 脂质体之间相似,但 SR-B1 依赖性似乎是 PC > PC/PA > PA 脂质体。我们的数据表明 (i) 纳米颗粒,包括高密度脂蛋白 (HDL)、二氧化硅、和脂质体与 SR-B1 的共同或接近位点结合,并且 (ii) PC/PA 和 PA 脂质体不仅与 SR-B1 结合,还与 HEK293T 细胞中的其他受体结合。此外,PC/PA 脂质体比 PC 脂质体更能诱导 HEK293T 细胞中的脂滴 (LD) 形成。用 SR-B1 siRNA 处理 HEK293T 细胞可抑制 PC/PA 脂质体诱导的 LD 形成。总之,我们的结果表明 SR-B1 在结合含 PC 的脂质体和随后诱导细胞反应中起着至关重要的作用,而 PA 可以调节它们。用 SR-B1 siRNA 处理 HEK293T 细胞可抑制 PC/PA 脂质体诱导的 LD 形成。总之,我们的结果表明 SR-B1 在结合含 PC 的脂质体和随后诱导细胞反应中起着至关重要的作用,而 PA 可以调节它们。用 SR-B1 siRNA 处理 HEK293T 细胞可抑制 PC/PA 脂质体诱导的 LD 形成。总之,我们的结果表明 SR-B1 在结合含 PC 的脂质体和随后诱导细胞反应中起着至关重要的作用,而 PA 可以调节它们。

更新日期:2021-04-22
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