Alves Isabel D, Jiao Chen-Yu, Aubry Soline, Aussedat Baptiste, Burlina Fabienne, Chassaing Gérard, Sagan Sandrine
Université Pierre et Marie Curie, Paris, France.
Biochim Biophys Acta. 2010 Dec;1798(12):2231-9. doi: 10.1016/j.bbamem.2010.02.009. Epub 2010 Feb 10.
Although cell-penetrating peptides are widely used as molecular devices to cross membranes and transport molecules or nanoparticles inside cells, the underlying internalization mechanism for such behavior is still studied and discussed. One of the reasons for such a debate is the wide panel of chemically different cell-penetrating peptides or cargo that is used. Indeed the intrinsic physico-chemical properties of CPP and conjugates strongly affect the cell membrane recognition and therefore the internalization pathways. Altogether, the mechanisms described so far should be shared between two general pathways: endocytosis and direct translocation. As it is established now that one cell-penetrating peptide can internalize at the same time by these two different pathways, the balance between the two pathways relies on the binding of the cell-penetrating peptide or conjugate to specific cell membrane components (carbohydrates, lipids). Like endocytosis which includes clathrin- and caveolae-dependent processes and macropinocytosis, different translocation mechanisms could co-exist, an idea that emerges from recent studies. In this review, we will focus solely on penetratin membrane interactions and internalization mechanisms.
尽管细胞穿透肽作为跨膜以及在细胞内运输分子或纳米颗粒的分子工具被广泛应用，但其内化机制仍在研究和讨论之中。产生这种争论的原因之一是所使用的细胞穿透肽或货物在化学性质上种类繁多。实际上，细胞穿透肽及其缀合物的内在物理化学性质会强烈影响细胞膜识别，进而影响内化途径。总体而言，目前所描述的机制可分为两种一般途径：内吞作用和直接转位。鉴于现已确定一种细胞穿透肽可同时通过这两种不同途径内化，这两种途径之间的平衡取决于细胞穿透肽或其缀合物与特定细胞膜成分（碳水化合物、脂质）的结合。如同内吞作用包括网格蛋白依赖性和小窝依赖性过程以及巨胞饮作用一样，不同的转位机制可能同时存在，这一观点源于最近的研究。在本综述中，我们将仅关注穿膜肽的膜相互作用和内化机制。
