Futaki S, Nakase I, Tadokoro A, Takeuchi T, Jones A T
Institute for Chemical Research, Kyoto University, Uji, Kyoto 611-0011, Japan.
Biochem Soc Trans. 2007 Aug;35(Pt 4):784-7. doi: 10.1042/BST0350784.
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 CPPs. 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.
随着细胞穿透肽（CPPs）作为细胞内递送载体的多功能性和应用已被广泛接受，使其有效内化的细胞摄取机制已成为备受关注的主题。富含精氨酸的肽，包括HIV-1转录激活肽（Tatp），被视为一类具有代表性的CPPs。有证据表明，巨胞饮作用在这些肽的细胞摄取中起关键作用。我们最近发现，用富含精氨酸的肽处理细胞会诱导Rac蛋白激活，从而导致丝状肌动蛋白（F-actin）的组织和巨胞饮作用。我们还发现，膜相关蛋白聚糖的消耗会导致该信号通路失效，这表明膜相关蛋白聚糖可能作为诱导富含精氨酸的肽进行巨胞饮摄取的潜在受体。然而，当在低温下或通过胆固醇消耗抑制巨胞饮途径时，这些肽可以通过其他机制内化，其中一种机制似乎是肽直接穿过质膜进行转运。本综述总结了目前关于富含精氨酸的肽内化的内吞和非内吞方面的理论。
