by Keyword: Clathrin
Monteil, VM, Wright, SC, Dyczynski, M, Kellner, MJ, Appelberg, S, Platzer, SW, Ibrahim, A, Kwon, H, Pittarokoilis, I, Mirandola, M, Michlits, G, Devignot, S, Elder, E, Abdurahman, S, Bereczky, S, Bagci, B, Youhanna, S, Aastrup, T, Lauschke, VM, Salata, C, Elaldi, N, Weber, F, Monserrat, N, Hawman, DW, Feldmann, H, Horn, M, Penninger, JM, Mirazimi, A, (2024). Crimean-Congo haemorrhagic fever virus uses LDLR to bind and enter host cells Nature Microbiology 9, 1499-1512 
Climate change and population densities accelerated transmission of highly pathogenic viruses to humans, including the Crimean-Congo haemorrhagic fever virus (CCHFV). Here we report that the Low Density Lipoprotein Receptor (LDLR) is a critical receptor for CCHFV cell entry, playing a vital role in CCHFV infection in cell culture and blood vessel organoids. The interaction between CCHFV and LDLR is highly specific, with other members of the LDLR protein family failing to bind to or neutralize the virus. Biosensor experiments demonstrate that LDLR specifically binds the surface glycoproteins of CCHFV. Importantly, mice lacking LDLR exhibit a delay in CCHFV-induced disease. Furthermore, we identified the presence of Apolipoprotein E (ApoE) on CCHFV particles. Our findings highlight the essential role of LDLR in CCHFV infection, irrespective of ApoE presence, when the virus is produced in tick cells. This discovery holds profound implications for the development of future therapies against CCHFV. Laboratory and clinical strains of Crimean-Congo haemorrhagic fever virus use LDLR to bind and enter host cells in blood vessel organoids and mice. Infection can also occur through ApoE, possibly present on virus particles.
JTD Keywords: Cholesterol, Clathrin, Entry requires, Genetics, Localization, Protei, Receptor
Solomon, M, Loeck, M, Silva-Abreu, M, Moscoso, R, Bautista, R, Vigo, M, Muro, S, (2022). Altered blood-brain barrier transport of nanotherapeutics in lysosomal storage diseases Journal Of Controlled Release 349, 1031-1044
Treatment of neurological lysosomal storage disorders (LSDs) are limited because of impermeability of the blood-brain barrier (BBB) to macromolecules. Nanoformulations targeting BBB transcytosis are being explored, but the status of these routes in LSDs is unknown. We studied nanocarriers (NCs) targeted to the transferrin receptor (TfR), ganglioside GM1 or ICAM1, associated to the clathrin, caveolar or cell adhesion molecule (CAM) routes, respectively. We used brain endothelial cells and mouse models of acid sphingomyelinase-deficient Niemann Pick disease (NPD), and postmortem LSD patients' brains, all compared to respective controls. NC transcytosis across brain endothelial cells and brain distribution in mice were affected, yet through different mechanisms. Reduced TfR and clathrin expression were found, along with decreased transcytosis in cells and mouse brain distribution. Caveolin-1 expression and GM1 transcytosis were also reduced, yet increased GM1 levels seemed to compensate, providing similar NC brain distribution in NPD vs. control mice. A tendency to lower NHE-1 levels was seen, but highly increased ICAM1 expression in cells and human brains correlated with increased transcytosis and brain distribution in mice. Thus, transcytosis-related alterations in NPD and likely other LSDs may impact therapeutic access to the brain, illustrating the need for these mechanistic studies.Copyright © 2022 Elsevier B.V. All rights reserved.
JTD Keywords: acid sphingomyelinase, antibody-affinity, blood -brain barrier, drug-delivery, icam-1-targeted nanocarriers, in-vivo, mediated endocytosis, model, neurological diseases, niemann-pick, targeted nanocarriers, trafficking, transcytosis pathways, Animals, Blood-brain barrier, Brain, Caveolin 1, Central-nervous-system, Clathrin, Endothelial cells, G(m1) ganglioside, Humans, Lysosomal storage diseases, Lysosomal storage disorders, Mice, Neurological diseases, Receptors, transferrin, Sphingomyelin phosphodiesterase, Targeted nanocarriers, Transcytosis, Transcytosis pathways
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.
JTD Keywords: Clathrin-mediated endocytosis, Optopharmacology, Peptides, Photoswitches, Protein-protein interactions
