Arginine-rich peptides and their internalization mechanisms
Arginine-rich peptides and their internalization mechanisms
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DOI：
10.1042/bst0350784
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发表时间：
2007-08-01
影响因子：
3.9
通讯作者：
Jones, A. T.
中科院分区：
文献类型：
--
作者：
Futaki, S.;Nakase, I.;Jones, A. T.
随着 CPP（细胞穿透肽）作为细胞内递送载体的多功能性和用途已被广泛接受，使其有效内化的细胞摄取机制已成为人们广泛关注的主题。富含精氨酸的肽，包括HIV-1 Tatp（转录肽反式激活因子），被认为是UPS的代表类别。有证据表明巨胞饮作用在这些肽的细胞摄取中起着至关重要的作用。我们最近发现，用富含精氨酸的肽处理细胞会诱导 Rac 蛋白的激活，从而导致 F-肌动蛋白（丝状肌动蛋白）组织和巨胞饮作用。我们还表明，膜相关蛋白聚糖的耗竭会导致该信号传导途径的失败，这表明膜相关蛋白聚糖可能充当诱导巨胞饮摄取富含精氨酸的肽的潜在受体。然而，当巨胞饮途径在低温或胆固醇消耗受到抑制时，这些肽可以通过替代机制内化，其中之一似乎是肽通过质膜直接易位。本综述总结了有关富含精氨酸肽内化的内吞和非内吞方面的当前理论。
As the versatility and use of CPPs (cell-penetrating peptides) as intracellular delivery vectors have been widely accepted, the cellular uptake mechanisms that enable their efficient internalization have become the subject of much interest. Arginine-rich peptides, including HIV-1 Tatp (transactivator of transcription peptide), are regarded as a representative class of UPS. Evidence suggests that macropinocytosis plays a crucial role in the cellular uptake of these peptides. we have recently shown that treatment of cells with arginine-rich peptides induces activation of Rac protein leading to F-actin (filamentous actin) organization and macropinocytosis. We have also shown that depletion of membrane-associated proteoglycans results in the failure of this signalling pathway, suggesting that membrane-associated proteoglycans may act as a potential receptor for the induction of macropinocytic uptake of arginine-rich peptides. However, when the macropinocytic pathway is inhibited at a low temperature or by cholesterol depletion, these peptides can be internalized by alternative mechanisms, one of which appears to be direct translocation of the peptides through the plasma membrane. This review summarizes the current theories on both endocytic and non-endocytic aspects of internalization of arginine-rich peptides.