Reinterpretation of the localization of the ATP binding cassette transporter ABCG1 in insulin-secreting cells and insights regarding its trafficking and function.
Reinterpretation of the localization of the ATP binding cassette transporter ABCG1 in insulin-secreting cells and insights regarding its trafficking and function.
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DOI：
10.1371/journal.pone.0198383
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发表时间：
2018
期刊：
影响因子：
3.7
通讯作者：
Castle JD
中科院分区：
文献类型：
--
作者：
Harris MT;Hussain SS;Inouye CM;Castle AM;Castle JD
ABC转运蛋白Abcg1参与调节细胞内胆固醇的外流和胆固醇在细胞内的分布。我们以前发现Abcg1缺乏抑制胰岛β细胞的胰岛素分泌，并基于其对胰岛素颗粒的免疫定位，提出了Abcg1在形成富含胆固醇的颗粒膜中的重要作用。虽然我们在其他地方证实了Abcg1与ABCA1和氧固醇结合蛋白OSBP一起支持胰岛素颗粒的形成，但这里的目的是澄清Abcg1在胰岛素分泌细胞中的定位，并提供关于Abcg1的S运输和功能位点的更多信息。我们发现，稳定表达的GFP标记的Abcg1与内源性Abcg1在胰腺INS1细胞中的分布非常相似，并聚集在跨高尔基网络(TGN)、内小体循环室(ERC)和细胞表面，而不是胰岛素颗粒、早期或晚期的内小体。值得注意的是，Abcg1是短暂的，蛋白酶体和溶酶体抑制剂都会减少它的降解。蛋白质合成受阻后，GFP标记的Abcg1首先从内质网和TGN消失，然后从ERC和质膜消失。除了有助于颗粒的形成外，我们的发现还提出了Abcg1可能在TGN之外调节涉及内吞途径的活动的可能性，特别是当Abcg1缺陷细胞中转铁蛋白受体的数量增加时。因此，Abcg1可能在细胞内的多个位置和质膜上作为胆固醇分布、膜转运和胆固醇外流的漫游传感器和调节器发挥作用。
The ABC transporter ABCG1 contributes to the regulation of cholesterol efflux from cells and to the distribution of cholesterol within cells. We showed previously that ABCG1 deficiency inhibits insulin secretion by pancreatic beta cells and, based on its immunolocalization to insulin granules, proposed its essential role in forming granule membranes that are enriched in cholesterol. While we confirm elsewhere that ABCG1, alongside ABCA1 and oxysterol binding protein OSBP, supports insulin granule formation, the aim here is to clarify the localization of ABCG1 within insulin-secreting cells and to provide added insight regarding ABCG1’s trafficking and sites of function. We show that stably expressed GFP-tagged ABCG1 closely mimics the distribution of endogenous ABCG1 in pancreatic INS1 cells and accumulates in the trans-Golgi network (TGN), endosomal recycling compartment (ERC) and on the cell surface but not on insulin granules, early or late endosomes. Notably, ABCG1 is short-lived, and proteasomal and lysosomal inhibitors both decrease its degradation. Following blockade of protein synthesis, GFP-tagged ABCG1 first disappears from the ER and TGN and later from the ERC and plasma membrane. In addition to aiding granule formation, our findings raise the prospect that ABCG1 may act beyond the TGN to regulate activities involving the endocytic pathway, especially as the amount of transferrin receptor is increased in ABCG1-deficient cells. Thus, ABCG1 may function at multiple intracellular sites and the plasma membrane as a roving sensor and modulator of cholesterol distribution, membrane trafficking and cholesterol efflux.
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影响因子：
7.7
作者：
Kruit JK;Wijesekara N;Westwell-Roper C;Vanmierlo T;de Haan W;Bhattacharjee A;Tang R;Wellington CL;LütJohann D;Johnson JD;Brunham LR;Verchere CB;Hayden MR
通讯作者：
Hayden MR
胰腺β细胞未成熟分泌颗粒中蛋白质分类的不同分子机制。
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作者：
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作者：
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通讯作者：
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影响因子：
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通讯作者：
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影响因子：
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作者：
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通讯作者：
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