The membrane repair response masks membrane disturbances caused by cell-penetrating peptide uptake
The membrane repair response masks membrane disturbances caused by cell-penetrating peptide uptake
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DOI：
10.1096/fj.08-110254
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发表时间：
2009-01-01
期刊：
影响因子：
4.8
通讯作者：
Hallbrink, Mattias
中科院分区：
文献类型：
--
作者：
Palm-Apergi, Caroline;Lorents, Annely;Hallbrink, Mattias
尽管细胞穿透肽能够将货物递送到细胞中，但其摄取机制仍不完全清楚，需要阐明以提高其递送效率。在这里，我们提出了一个新的机制，参与吸收，膜修复反应的证据。最近的研究表明，可能有一个直接渗透的肽平行于不同形式的内吞作用。然而，亲水性肽通过疏水性质膜的直接渗透是非常有争议的。三种参与靶细胞凋亡的蛋白质-穿孔素、颗粒溶素和颗粒酶-在细胞穿透肽的摄取中具有许多共同的特征（例如，例如，在一个实施例中，它们结合蛋白聚糖）。在穿孔素摄取过程中，由于细胞外钙离子内流，该蛋白激活膜修复反应，这是在质膜受损的细胞中触发的重新密封机制。在激活膜修复反应时，内部囊泡被动员到被破坏的质膜的位点，在几秒钟内重新密封它。在这项研究中，我们使用流式细胞术，荧光和电子显微镜，以及高效液相色谱和质谱，来证明膜修复反应能够掩盖细胞穿透肽摄取过程中造成的损伤，从而防止内源性分子泄漏出细胞。Palm-Palmgi角，Lorents，A.，Padari，K.，Pooga，M.，和Hallbrink，M.膜修复反应掩盖了由细胞穿透肽摄取引起的膜干扰。FASEB J. 23，214-223（2009）
Although cell-penetrating peptides are able to deliver cargo into cells, their uptake mechanism is still not fully understood and needs to be elucidated to improve their delivery efficiency. Herein, we present evidence of a new mechanism involved in uptake, the membrane repair response. Recent studies have suggested that there might be a direct penetration of peptides in parallel with different forms of endocytosis. The direct penetration of hydrophilic peptides through the hydrophobic plasma membrane, however, is highly controversial. Three proteins involved in target cell apoptosis-perforin, granulysin, and granzymes-share many features common in uptake of cell-penetrating peptides (e. g., they bind proteoglycans). During perforin uptake, the protein activates the membrane repair response, a resealing mechanism triggered in cells with injured plasma membrane, because of extracellular calcium influx. On activation of the membrane repair response, internal vesicles are mobilized to the site of the disrupted plasma membrane, resealing it within seconds. In this study, we have used flow cytometry, fluorescence, and electron microscopy, together with high-performance liquid chromatography and mass spectrometry, to present evidence that the membrane repair response is able to mask damages caused during cell-penetrating peptide uptake, thus preventing leakage of endogenous molecules out of the cell.-Palm-Apergi, C., Lorents, A., Padari, K., Pooga, M., and Hallbrink, M. The membrane repair response masks membrane disturbances caused by cell-penetrating peptide uptake. FASEB J. 23, 214-223 (2009)