Author:
Goncharuk Sergey A.,Artemieva Lilya E.,Nadezhdin Kirill D.,Arseniev Alexander S.,Mineev Konstantin S.
Abstract
AbstractThe neurotrophin receptor p75NTR plays crucial roles in neuron development and regulates important neuronal processes like degeneration, apoptosis and cell survival. At the same time the detailed mechanism of signal transduction is unclear. One of the main hypotheses known as the snail-tong mechanism assumes that in the inactive state, the death domains interact with each other and in response to ligand binding there is a conformational change leading to their exposure. Here, we show that neither rat nor human p75NTR death domains homodimerize in solution. Moreover, there is no interaction between the death domains in a more native context: the dimerization of transmembrane domains in liposomes and the presence of activating mutation in extracellular juxtamembrane region do not lead to intracellular domain interaction. These findings suggest that the activation mechanism of p75NTR should be revised. Thus, we propose a novel model of p75NTR functioning based on interaction with “helper” protein.
Funder
Russian Science Foundation
Publisher
Springer Science and Business Media LLC
Reference59 articles.
1. Bibel, M. & Barde, Y.-A. Neurotrophins: Key regulators of cell fate and cell shape in the vertebrate nervous system. Genes Dev.14, 2919–2937 (2000).
2. Chao, M. V. Neurotrophins and their receptors: A convergence point for many signalling pathways. Nat. Rev. Neurosci.4, 299–309 (2003).
3. Ibáñez, C. F. & Simi, A. p75 neurotrophin receptor signaling in nervous system injury and degeneration: Paradox and opportunity. Trends Neurosci.35, 431–440 (2012).
4. Lee, R., Kermani, P., Teng, K. K. & Hempstead, B. L. Regulation of cell survival by secreted proneurotrophins. Science294, 1945–1948 (2001).
5. Vicario, A., Kisiswa, L., Tann, J. Y., Kelly, C. E. & Ibáñez, C. F. Neuron-type-specific signaling by the p75NTR death receptor is regulated by differential proteolytic cleavage. J. Cell. Sci.128, 1507–1517 (2015).
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