by Keyword: Endocytosis

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Muro, Silvia, (2018). Alterations in cellular processes involving vesicular trafficking and implications in drug delivery Biomimetics 3, (3), 19

Endocytosis and vesicular trafficking are cellular processes that regulate numerous functions required to sustain life. From a translational perspective, they offer avenues to improve the access of therapeutic drugs across cellular barriers that separate body compartments and into diseased cells. However, the fact that many factors have the potential to alter these routes, impacting our ability to effectively exploit them, is often overlooked. Altered vesicular transport may arise from the molecular defects underlying the pathological syndrome which we aim to treat, the activity of the drugs being used, or side effects derived from the drug carriers employed. In addition, most cellular models currently available do not properly reflect key physiological parameters of the biological environment in the body, hindering translational progress. This article offers a critical overview of these topics, discussing current achievements, limitations and future perspectives on the use of vesicular transport for drug delivery applications.

Keywords: Cellular vesicles, Vesicle fusion, Fission and intracellular trafficking, Drug delivery systems and nanomedicines, Transcytosis and endocytosis of drugs carriers, Disease effects on vesicular trafficking, Drug effects on vesicular trafficking, Role of the biological environment

Hervera, A., De Virgiliis, F., Palmisano, I., Zhou, L., Tantardini, E., Kong, G., Hutson, T., Danzi, M. C., Perry, R. B. T., Santos, C. X. C., Kapustin, A. N., Fleck, R. A., Del Río, J. A., Carroll, T., Lemmon, V., Bixby, J. L., Shah, A. M., Fainzilber, M., Di Giovanni, S., (2018). Reactive oxygen species regulate axonal regeneration through the release of exosomal NADPH oxidase 2 complexes into injured axons Nature Cell Biology 20, (3), 307-319

Reactive oxygen species (ROS) contribute to tissue damage and remodelling mediated by the inflammatory response after injury. Here we show that ROS, which promote axonal dieback and degeneration after injury, are also required for axonal regeneration and functional recovery after spinal injury. We find that ROS production in the injured sciatic nerve and dorsal root ganglia requires CX3CR1-dependent recruitment of inflammatory cells. Next, exosomes containing functional NADPH oxidase 2 complexes are released from macrophages and incorporated into injured axons via endocytosis. Once in axonal endosomes, active NOX2 is retrogradely transported to the cell body through an importin-β1–dynein-dependent mechanism. Endosomal NOX2 oxidizes PTEN, which leads to its inactivation, thus stimulating PI3K–phosporylated (p-)Akt signalling and regenerative outgrowth. Challenging the view that ROS are exclusively involved in nerve degeneration, we propose a previously unrecognized role of ROS in mammalian axonal regeneration through a NOX2–PI3K–p-Akt signalling pathway.

Keywords: Adult neurogenesis, Endocytosis, Exocytosis, Monocytes and macrophages, Stress signalling

Nevola, L., Martín-Quirós, A., Eckelt, K., Camarero, N., Tosi, S., Llobet, A., Giralt, E., Gorostiza, P., (2013). Light-regulated stapled peptides to inhibit protein-protein interactions involved in clathrin-mediated endocytosis Angewandte Chemie - International Edition , 52, (30), 7704-7708

Control of membrane traffic: Photoswitchable inhibitors of protein-protein interactions were applied to photoregulate clathrin-mediated endocytosis (CME) in living cells. Traffic light (TL) peptides acting as "stop" and "go" signals for membrane traffic can be used to dissect the role of CME in receptor internalization and in cell growth, division, and differentiation.

Keywords: Clathrin-mediated endocytosis, Optopharmacology, Peptides, Photoswitches, Protein-protein interactions