The DOI matches its Crossref record; 6 of the 6 references it cites were found in a registry or an index.
An endocytosis pathway initiated through neuropilin-1 and regulated by nutrient availability
Open accessAbstract
Neuropilins (NRPs) are trans-membrane receptors involved in axon guidance and vascular development. Many growth factors and other signalling molecules bind to NRPs through a carboxy (C)-terminal, basic sequence motif (C-end Rule or CendR motif). Peptides with this motif (CendR peptides) are taken up into cells by endocytosis. Tumour-homing CendR peptides penetrate through tumour tissue and have shown utility in enhancing drug delivery into tumours. Here we show, using RNAi screening and subsequent validation studies, that NRP1-mediated endocytosis of CendR peptides is distinct from known endocytic pathways. Ultrastructurally, CendR endocytosis resembles macropinocytosis, but is mechanistically different. We also show that nutrient-sensing networks such as mTOR signalling regulate CendR endocytosis and subsequent intercellular transport of CendR cargo, both of which are stimulated by nutrient depletion. As CendR is a bulk transport pathway, our results suggest a role for it in nutrient transport; CendR-enhanced drug delivery then makes use of this natural pathway. CendR peptides, based on a C-terminal motif found in neuropilins, have been used to promote drug delivery to tumours by endocytosis. Pang et al. show that CendR peptides are taken up by a mechanistically distinct form of endocytosis that resembles macropinocytosis, and is stimulated by nutrient depletion.
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Cites
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Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells
Commisso, C., Davidson, S. M., Soydaner-Azeloglu, R. G., Parker, S. J., Kamphorst, J. J., Hackett, S., Grabocka, E., Nofal, M., Drebin, J. A., Thompson, C. B., et al. (2013) · Nature · doi:10.1038/nature12138 · Cited by 1,683
C-end rule peptides mediate neuropilin-1-dependent cell, vascular, and tissue penetration
Teesalu, T., Sugahara, K. N., Kotamraju, V. R., & Ruoslahti, E. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0908201106 · Cited by 812
Self-citationInhibitory effect of mTOR activator MHY1485 on autophagy: suppression of lysosomal fusion
Choi, Y. J., Park, Y. J., Park, J. Y., Jeong, H. O., Kim, D. H., Ha, Y. M., Kim, J. M., Song, Y. M., Heo, H.-S., Yu, B. P., et al. (2012) · PLoS ONE · doi:10.1371/journal.pone.0043418 · Cited by 192
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Neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity
Cantuti-Castelvetri, L., Ojha, R., Pedro, L. D., Djannatian, M., Franz, J., Kuivanen, S., van der Meer, F., Kallio, K., Kaya, T., Anastasina, M., et al. (2020) · Science · doi:10.1126/science.abd2985 · Cited by 1,925
Self-citationNeuropilin-1 is a host factor for SARS-CoV-2 infection
Daly, J. L., Simonetti, B., Klein, K., Chen, K.-E., Williamson, M. K., Antón-Plágaro, C., Shoemark, D. K., Simón-Gracia, L., Bauer, M., Hollandi, R., et al. (2020) · Science · doi:10.1126/science.abd3072 · Cited by 1,251
Self-citationTheranostic Fluorescent Probes
Sharma, A., Verwilst, P., Li, M., Ma, D., Singh, N., Yoo, J., Kim, Y., Yang, Y., Zhu, J.-H., Huang, H., et al. (2024) · Chemical Reviews · doi:10.1021/acs.chemrev.3c00778 · Cited by 499
Tumor penetrating peptides for improved drug delivery
Ruoslahti, E. (2017) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.03.008 · Cited by 459
Self-citationEl-Sawy, H. S., Al-Abd, A. M., Ahmed, T. A., El-Say, K. M., & Torchilin, V. P. (2018) · ACS Nano · doi:10.1021/acsnano.8b06104 · Cited by 431
Metadata
- Authors
- Pang, H.-B., Braun, G. B., Friman, T., Aza-Blanc, P., Ruidiaz, M. E., Sugahara, K. N., Teesalu, T., & Ruoslahti, E.
- Venue
- Nature Communications
- Published
- 2014-10-03
- Volume
- 5
- Issue
- 1
- Pages
- 4904-4904
- ISSN
- 2041-1723 (ISSN-L)
- OpenAlex
- W1981988157
- Cited by
- 195
- References
- 6
- FWCI
- 6.38
- Type
- journal article
- Language
- en
- Open access
- bronze
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