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Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins

Tunneling nanotubes (TNTs), intercellular connections enriched with F-actin, were first identified as a viable means of cellular communication and organelle transport in animal cells at the early part of this century. Within the last 10 years, these microscopic and highly dynamic protrusions have be...

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Autor principal: Lagalwar, Sarita
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336677/
https://www.ncbi.nlm.nih.gov/pubmed/35909452
http://dx.doi.org/10.3389/fnmol.2022.957067
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author Lagalwar, Sarita
author_facet Lagalwar, Sarita
author_sort Lagalwar, Sarita
collection PubMed
description Tunneling nanotubes (TNTs), intercellular connections enriched with F-actin, were first identified as a viable means of cellular communication and organelle transport in animal cells at the early part of this century. Within the last 10 years, these microscopic and highly dynamic protrusions have been implicated in neurodegenerative disease propagation and pathogenesis. A host of aggregation-prone protein inclusions, including those containing alpha-synuclein, tau, prions and others, hijack this communication mechanism in both neurons and astrocytes. The exact cellular mechanisms underlying TNT-based propagation remain largely unknown, however, common practices can be identified. First, selective expression of the aggregation-prone form of proteins increases TNT density; next, endo-lysosomal pathways appear to support the loading and unloading of protein onto the TNT; and finally, TNT assembly results in the spontaneous formation of aggregation-prone protein inclusions in “acceptor” cells, indicating that TNTs are involved in not only the transport of inclusions but also in the seeding of new inclusions in naïve cells. These observations have implications for the spreading of neurodegenerative disease in the central nervous system and the consequent progression of symptoms. Here, I will summarize the empirical evidence of TNT-based aggregation-prone protein propagation to date, and propose an inclusive model of aggregate inclusion propagation along TNTs.
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spelling pubmed-93366772022-07-30 Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins Lagalwar, Sarita Front Mol Neurosci Molecular Neuroscience Tunneling nanotubes (TNTs), intercellular connections enriched with F-actin, were first identified as a viable means of cellular communication and organelle transport in animal cells at the early part of this century. Within the last 10 years, these microscopic and highly dynamic protrusions have been implicated in neurodegenerative disease propagation and pathogenesis. A host of aggregation-prone protein inclusions, including those containing alpha-synuclein, tau, prions and others, hijack this communication mechanism in both neurons and astrocytes. The exact cellular mechanisms underlying TNT-based propagation remain largely unknown, however, common practices can be identified. First, selective expression of the aggregation-prone form of proteins increases TNT density; next, endo-lysosomal pathways appear to support the loading and unloading of protein onto the TNT; and finally, TNT assembly results in the spontaneous formation of aggregation-prone protein inclusions in “acceptor” cells, indicating that TNTs are involved in not only the transport of inclusions but also in the seeding of new inclusions in naïve cells. These observations have implications for the spreading of neurodegenerative disease in the central nervous system and the consequent progression of symptoms. Here, I will summarize the empirical evidence of TNT-based aggregation-prone protein propagation to date, and propose an inclusive model of aggregate inclusion propagation along TNTs. Frontiers Media S.A. 2022-07-15 /pmc/articles/PMC9336677/ /pubmed/35909452 http://dx.doi.org/10.3389/fnmol.2022.957067 Text en Copyright © 2022 Lagalwar. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Molecular Neuroscience
Lagalwar, Sarita
Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
title Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
title_full Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
title_fullStr Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
title_full_unstemmed Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
title_short Mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
title_sort mechanisms of tunneling nanotube-based propagation of neurodegenerative disease proteins
topic Molecular Neuroscience
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9336677/
https://www.ncbi.nlm.nih.gov/pubmed/35909452
http://dx.doi.org/10.3389/fnmol.2022.957067
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