Impact of the Endosomal Escape Activity of Cell-Penetrating Peptides on the Endocytic Pathway.
Impact of the Endosomal Escape Activity of Cell-Penetrating Peptides on the Endocytic Pathway.
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DOI：
10.1021/acschembio.0c00319
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发表时间：
2020-09-18
影响因子：
4
通讯作者：
Pellois JP
中科院分区：
文献类型：
--
作者：
Kondow-McConaghy HM;Muthukrishnan N;Erazo-Oliveras A;Najjar K;Juliano RL;Pellois JP
细胞穿透肽（CPP）通常用于将大分子递送到活的人类细胞中。为了进入细胞的胞质空间，CPP通常使内体的膜透化。反过来，已经开发了几种方法来增加CPP的内体膜渗透活性，从而提高递送效率。然而，内吞途径在维持细胞内稳态中是重要的，并且理解内体渗透如何影响细胞现在对于定义CPP的一般效用至关重要。在这里，我们调查如何CPP为基础的交付协议影响的内吞网络。我们发现，在某些情况下，细胞渗透诱导激活的Chmp 1b，半乳糖凝集素-3，TFEB，组件的内体修复，细胞器清除，和生物合成途径，分别。我们还检测到细胞递送调节内吞作用和内吞蛋白水解。值得注意的是，原型CPP达特的多聚体类似物有效地透化内体而不诱导膜损伤反应。这些结果挑战了使内体泄漏的试剂通常是有毒的这一观点。相反，我们的数据表明，有可能以最小的有害影响进入细胞。
Cell-penetrating peptides (CPPs) are routinely used for the delivery of macromolecules into live human cells. To enter the cytosolic space of cells, CPPs typically permeabilize the membrane of endosomes. In turn, several approaches have been developed to increase the endosomal membrane permeation activity of CPPs so as to improve delivery efficiencies. The endocytic pathway is however important in maintaining cellular homeostasis and understanding how endosomal permeation impacts cells is now critical to define the general utility of CPPs. Herein, we investigate how CPP-based delivery protocols affect the endocytic network. We detect that in some cases, cell penetration induces the activation of Chmp1b, Galectin-3, and TFEB, components of endosomal repair, organelle clearance, and biogenesis pathways, respectively. We also detect that cellular delivery modulates endocytosis and endocytic proteolysis. Remarkably, a multimeric analog of the prototypical CPP TAT permeabilizes endosomes efficiently without inducing membrane damage responses. These results challenge the notion that reagents that make endosomes leaky are generally toxic. Instead, our data indicates that it is possible to enter cells with minimal deleterious effects.
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DOI：
10.1126/science.aar5078
发表时间：
2018-04-06
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Skowyra ML;Schlesinger PH;Naismith TV;Hanson PI
通讯作者：
Hanson PI
影响因子：
21.3
作者：
Medina DL;Di Paola S;Peluso I;Armani A;De Stefani D;Venditti R;Montefusco S;Scotto-Rosato A;Prezioso C;Forrester A;Settembre C;Wang W;Gao Q;Xu H;Sandri M;Rizzuto R;De Matteis MA;Ballabio A
通讯作者：
Ballabio A
DOI：
10.3390/ph5111177
发表时间：
2012-11-01
期刊：
Pharmaceuticals (Basel, Switzerland)
影响因子：
--
作者：
Erazo-Oliveras A;Muthukrishnan N;Baker R;Wang TY;Pellois JP
通讯作者：
Pellois JP
影响因子：
4
作者：
Allen, Jason;Najjar, Kristina;Pellois, Jean-Philippe
通讯作者：
Pellois, Jean-Philippe
影响因子：
7
作者：
Ramakrishna S;Kwaku Dad AB;Beloor J;Gopalappa R;Lee SK;Kim H
通讯作者：
Kim H