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The membrane repair response masks membrane disturbances caused by cell‐penetrating peptide uptake
Author(s) -
PalmApergi Caroline,
Lorents Annely,
Padari Kart,
Pooga Margus
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.08-110254
Subject(s) - cell penetrating peptide , microbiology and biotechnology , chemistry , exocytosis , granzyme , cell membrane , endocytosis , membrane , biophysics , cell , perforin , peptide , biochemistry , biology , cytotoxicity , in vitro
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 sug‐gested that there might be a direct penetration of peptides in parallel with different forms of endocyto‐sis. The direct penetration of hydrophilic peptides through the hydrophobic plasma membrane, however, is highly controversial. Three proteins involved in tar‐get cell apoptosis—perforin, granulysin, and gran‐zymes—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 mem‐brane, resealing it within seconds. In this study, we have used flow cytometry, fluorescence, and electron microscopy, together with high‐performance liquid chroma‐tography and mass spectrometry, to present evidence that the membrane repair response is able to mask damages caused during cell‐penetrating peptide up‐take, 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)