caa a22 4500 606176616 CHVBK 20210128100748.0 cr unu---uuuuu 210128e20150201xx s 000 0 eng 10.1007/s00018-014-1696-y doi (NATIONALLICENCE)springer-10.1007/s00018-014-1696-y Massive glycosaminoglycan-dependent entry of Trp-containing cell-penetrating peptides induced by exogenous sphingomyelinase or cholesterol depletion [Elektronische Daten] [Chérine Bechara, Manjula Pallerla, Fabienne Burlina, Françoise Illien, Sophie Cribier, Sandrine Sagan] Among non-invasive cell delivery strategies, cell-penetrating peptide (CPP) vectors represent interesting new tools. To get fundamental knowledge about the still debated internalisation mechanisms of these peptides, we modified the membrane content of cells, typically by hydrolysis of sphingomyelin or depletion of cholesterol from the membrane outer leaflet. We quantified and visualised the effect of these viable cell surface treatments on the internalisation efficiency of different CPPs, among which the most studied Tat, R9, penetratin and analogues, that all carry the N-terminal biotin-Gly4 tag cargo. Under these cell membrane treatments, only penetratin and R6W3 underwent a massive glycosaminoglycan (GAG)-dependent entry in cells. Internalisation of the other peptides was only slightly increased, similarly in the absence or the presence of GAGs for R9, and only in the presence of GAGs for Tat and R6L3. Ceramide formation (or cholesterol depletion) is known to lead to the reorganisation of membrane lipid domains into larger platforms, which can serve as a trap and cluster receptors. These results show that GAG clustering, enhanced by formation of ceramide, is efficiently exploited by penetratin and R6W3, which contains Trp residues in their sequence but not Tat, R9 and R6L3. Hence, these data shed new lights on the differences in the internalisation mechanism and pathway of these peptides that are widely used in delivery of cargo molecules. Springer Basel, 2014 Ceramide-enriched domain nationallicence Endocytosis nationallicence Tryptophan-rich peptide nationallicence Arginine-rich peptide nationallicence Cationic peptide nationallicence Bechara Chérine Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut Pallerla Manjula Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut Burlina Fabienne Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut Illien Françoise Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut Cribier Sophie Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut Sagan Sandrine Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 809-820 1420-682X 72:4<809 2015 72 18 https://doi.org/10.1007/s00018-014-1696-y text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00018-014-1696-y text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Bechara Chérine Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut NATIONALLICENCE 700 1- Pallerla Manjula Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut NATIONALLICENCE 700 1- Burlina Fabienne Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut NATIONALLICENCE 700 1- Illien Françoise Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut NATIONALLICENCE 700 1- Cribier Sophie Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut NATIONALLICENCE 700 1- Sagan Sandrine Sorbonne Universités, UPMC Univ Paris 06, LBM, 4 Place Jussieu, 75005, Paris, France aut NATIONALLICENCE 773 0- Cellular and Molecular Life Sciences Springer Basel 72/4(2015-02-01), 809-820 1420-682X 72:4<809 2015 72 18