Utilizing HaloTag Technology to Track the Fate of PCSK9 from Intracellular vs. Extracellular Sources.
Utilizing HaloTag Technology to Track the Fate of PCSK9 from Intracellular vs. Extracellular Sources.
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DOI：
10.2174/1875397301206010038
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发表时间：
2012-01-01
期刊：
影响因子：
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通讯作者：
Ehrhardt, Anka G
中科院分区：
文献类型：
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作者：
Ai, Xi;Fischer, Paul;Ehrhardt, Anka G
特定蛋白质的功能取决于其定位和环境。追踪蛋白质“命运”的能力是阐明其功能的有价值的工具。我们利用HaloTag技术研究了人前蛋白转化酶枯草杆菌蛋白酶样Kexin 9型（PCSK 9）的定位和转归，PCSK 9在调节循环低密度脂蛋白胆固醇（LDL-c）水平中的作用归因于循环PCSK 9与LDL受体（LDLR）的结合以及随后的LDLR的溶酶体降解。然而，文献中的提示表明，细胞内PCSK 9可能在新合成蛋白的加工过程中作用于LDLR。为了解决这个问题，细胞内PCSK 9的来源和命运需要进一步的调查，我们应用HaloTag技术来区分细胞内PCSK 9的来源，并显示新合成的细胞内PCSK 9与重摄取后的PCSK 9具有独特的定位。这表明PCSK 9在与LDLR相互作用时具有不同的功能。
The function of a particular protein is dependent upon its localization and milieu. The ability to track the "fate" of a protein is a valuable tool to elucidate its function. We present the use of HaloTag technology to study the localization and fate of human Proprotein Convertase Subtilisin-like Kexin type 9 (PCSK9).The role of PCSK9 in the regulation of circulating low density lipoprotein-cholesterol (LDL-c) levels is ascribed to binding of circulating PCSK9 to the LDL receptor (LDLR) and subsequent lysosomal degradation of LDLR. However, hints in the literature indicate that intracellular PCSK9 may act on the LDLR, possibly during processing of newly synthesized protein. To address this question, the source and fate of intracellular PCSK9 requires further investigation.We applied HaloTag technology to distinguish the source of intracellular PCSK9 and showed that newly synthesized intracellular PCSK9 has unique localization from the PCSK9 after re-uptake. This suggests different functions of PCSK9 while interacting with the LDLR.