Cell-surface Accumulation of Flock House Virus-derived Peptide Leads to Efficient Internalization via Macropinocytosis
Cell-surface Accumulation of Flock House Virus-derived Peptide Leads to Efficient Internalization via Macropinocytosis
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DOI：
10.1038/mt.2009.192
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发表时间：
2009-11-01
影响因子：
12.4
通讯作者：
Futaki, Shiroh
中科院分区：
文献类型：
--
作者：
Nakase, Ikuhiko;Hirose, Hisaaki;Futaki, Shiroh
富含精氨酸的细胞穿透肽（CPP），包括人免疫缺陷病毒1型（HIV-1）达特（48-60）和寡聚腺苷酸，由于其内化到细胞中并穿透生物膜的能力，已被用作递送货物分子的载体。尽管已对其进行了广泛的研究，但有效地将清洁生产伙伴关系内部化所需的因素仍不清楚。在这份报告中，我们评估了来自DNA/RNA结合肽的7种CPP的内化效率，发现来自鸡群病毒（FHV）外壳蛋白的肽最有效地内化到中国仓鼠卵巢（CHO-K1）、HeLa和Jurkat细胞中。将促进内化的因素与达特肽的因素进行比较，揭示了FHV肽比达特肽更有效地诱导巨胞饮，这导致其高细胞摄取效率。此外，FHV肽通过糖胺聚糖（GAG）在细胞膜上的强吸附被证明是诱导巨胞饮的关键因素，并且这些步骤通过与肌动蛋白组织相关的肽内化到细胞中的实时成像被成功地监测。因此，FHV肽内化的显着方法突出了富含精氨酸的CPP内化的关键因素。
Arginine-rich cell-penetrating peptides (CPPs), including human immunodeficiency virus type 1 (HIV-1) Tat (48-60) and oligoarginines, have been applied as carriers for delivery of cargo molecules, because of their capacity to internalize into cells and penetrate biological membranes. Despite the fact that they have been extensively studied, the factors required for the efficient internalization of CPPs are still unclear. In this report, we evaluated the internalization efficiencies of seven CPPs derived from DNA/RNA-binding peptides, and discovered that a peptide derived from the flock house virus (FHV) coat protein was internalized most efficiently into Chinese hamster ovary (CHO-K1), HeLa, and Jurkat cells. Comparison of the factors facilitating the internalization with those of the Tat peptide revealed that the FHV peptide induces macropinocytosis much more efficiently than the Tat peptide, which leads to its high cellular uptake efficiency. Additionally, the strong adsorption of the FHV peptide on cell membranes via glycosaminoglycans (GAGs) was shown to be a key factor for induction of macropinocytosis, and these steps were successfully monitored by live imaging of the peptide internalization into cells in relation to the actin organization. The remarkable methods of FHV peptide internalization thus highlighted the critical factors for internalizations of the arginine-rich CPPs.