article published yes Xiaohe Tian author Diana M. Leite author Edoardo Scarpa author Sophie Nyberg author Gavin Fullstone author Joe Forth author Diana Matias author Azzurra Apriceno author Alessandro Poma author Aroa Duro-Castano author Manish Vuyyuru author Lena Harker-Kirschneck author Anđela Šarić author bf63d406-f056-11eb-b41d-f263a6566d8b0000-0002-7854-2139 Zhongping Zhang author Pan Xiang author Bin Fang author Yupeng Tian author Lei Luo author Loris Rizzello author Giuseppe Battaglia author The blood-brain barrier is made of polarized brain endothelial cells (BECs) phenotypically conditioned by the central nervous system (CNS). Although transport across BECs is of paramount importance for nutrient uptake as well as ridding the brain of waste products, the intracellular sorting mechanisms that regulate successful receptor-mediated transcytosis in BECs remain to be elucidated. Here, we used a synthetic multivalent system with tunable avidity to the low-density lipoprotein receptor–related protein 1 (LRP1) to investigate the mechanisms of transport across BECs. We used a combination of conventional and super-resolution microscopy, both in vivo and in vitro, accompanied with biophysical modeling of transport kinetics and membrane-bound interactions to elucidate the role of membrane-sculpting protein syndapin-2 on fast transport via tubule formation. We show that high-avidity cargo biases the LRP1 toward internalization associated with fast degradation, while mid-avidity augments the formation of syndapin-2 tubular carriers promoting a fast shuttling across. https://research-explorer.ista.ac.at/download/10342/10343/2020_SciAdv_Tian.pdf application/pdfno https://creativecommons.org/licenses/by/4.0/ American Association for the Advancement of Science2020 eng multidisciplinary 2375-2548 3324695310.1126/sciadv.abc4397 648 yes X. Tian, D.M. Leite, E. Scarpa, S. Nyberg, G. Fullstone, J. Forth, D. Matias, A. Apriceno, A. Poma, A. Duro-Castano, M. Vuyyuru, L. Harker-Kirschneck, A. Šarić, Z. Zhang, P. Xiang, B. Fang, Y. Tian, L. Luo, L. Rizzello, G. Battaglia, Science Advances 6 (2020). Tian, Xiaohe, et al. “On the Shuttling across the Blood-Brain Barrier via Tubule Formation: Mechanism and Cargo Avidity Bias.” <i>Science Advances</i>, vol. 6, no. 48, eabc4397, American Association for the Advancement of Science, 2020, doi:<a href="https://doi.org/10.1126/sciadv.abc4397">10.1126/sciadv.abc4397</a>. Tian, Xiaohe, Diana M. Leite, Edoardo Scarpa, Sophie Nyberg, Gavin Fullstone, Joe Forth, Diana Matias, et al. “On the Shuttling across the Blood-Brain Barrier via Tubule Formation: Mechanism and Cargo Avidity Bias.” <i>Science Advances</i>. American Association for the Advancement of Science, 2020. <a href="https://doi.org/10.1126/sciadv.abc4397">https://doi.org/10.1126/sciadv.abc4397</a>. Tian, X., Leite, D. M., Scarpa, E., Nyberg, S., Fullstone, G., Forth, J., … Battaglia, G. (2020). On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias. <i>Science Advances</i>. American Association for the Advancement of Science. <a href="https://doi.org/10.1126/sciadv.abc4397">https://doi.org/10.1126/sciadv.abc4397</a> X. Tian <i>et al.</i>, “On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias,” <i>Science Advances</i>, vol. 6, no. 48. American Association for the Advancement of Science, 2020. Tian X, Leite DM, Scarpa E, Nyberg S, Fullstone G, Forth J, Matias D, Apriceno A, Poma A, Duro-Castano A, Vuyyuru M, Harker-Kirschneck L, Šarić A, Zhang Z, Xiang P, Fang B, Tian Y, Luo L, Rizzello L, Battaglia G. 2020. On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias. Science Advances. 6(48), eabc4397. Tian X, Leite DM, Scarpa E, et al. On the shuttling across the blood-brain barrier via tubule formation: Mechanism and cargo avidity bias. <i>Science Advances</i>. 2020;6(48). doi:<a href="https://doi.org/10.1126/sciadv.abc4397">10.1126/sciadv.abc4397</a> 103422021-11-26T06:40:28Z2024-10-16T12:56:52Z