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Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria
Microtubule-based transport provides mitochondria to distant regions of neurons and is essential for neuronal health. To identify compounds that increase mitochondrial motility, we screened 1,641 small-molecules in a high-throughput screening platform. Indirubin and cantharidin increased mitochondri...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Frontiers Media S.A.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973303/ https://www.ncbi.nlm.nih.gov/pubmed/35370563 http://dx.doi.org/10.3389/fncel.2022.852245 |
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author | Heo, Keunjung Basu, Himanish Gutnick, Amos Wei, Wei Shlevkov, Evgeny Schwarz, Thomas L. |
author_facet | Heo, Keunjung Basu, Himanish Gutnick, Amos Wei, Wei Shlevkov, Evgeny Schwarz, Thomas L. |
author_sort | Heo, Keunjung |
collection | PubMed |
description | Microtubule-based transport provides mitochondria to distant regions of neurons and is essential for neuronal health. To identify compounds that increase mitochondrial motility, we screened 1,641 small-molecules in a high-throughput screening platform. Indirubin and cantharidin increased mitochondrial motility in rat cortical neurons. Cantharidin is known to inhibit protein phosphatase 2A (PP2A). We therefore tested two other inhibitors of PP2A: LB-100 and okadaic acid. LB-100 increased mitochondrial motility, but okadaic acid did not. To resolve this discrepancy, we knocked down expression of the catalytic subunit of PP2A (PP2CA). This long-term inhibition of PP2A more than doubled retrograde transport of axonal mitochondria, confirming the importance of PP2A as a regulator of mitochondrial motility and as the likely mediator of cantharidin’s effect. |
format | Online Article Text |
id | pubmed-8973303 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Frontiers Media S.A. |
record_format | MEDLINE/PubMed |
spelling | pubmed-89733032022-04-02 Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria Heo, Keunjung Basu, Himanish Gutnick, Amos Wei, Wei Shlevkov, Evgeny Schwarz, Thomas L. Front Cell Neurosci Neuroscience Microtubule-based transport provides mitochondria to distant regions of neurons and is essential for neuronal health. To identify compounds that increase mitochondrial motility, we screened 1,641 small-molecules in a high-throughput screening platform. Indirubin and cantharidin increased mitochondrial motility in rat cortical neurons. Cantharidin is known to inhibit protein phosphatase 2A (PP2A). We therefore tested two other inhibitors of PP2A: LB-100 and okadaic acid. LB-100 increased mitochondrial motility, but okadaic acid did not. To resolve this discrepancy, we knocked down expression of the catalytic subunit of PP2A (PP2CA). This long-term inhibition of PP2A more than doubled retrograde transport of axonal mitochondria, confirming the importance of PP2A as a regulator of mitochondrial motility and as the likely mediator of cantharidin’s effect. Frontiers Media S.A. 2022-03-18 /pmc/articles/PMC8973303/ /pubmed/35370563 http://dx.doi.org/10.3389/fncel.2022.852245 Text en Copyright © 2022 Heo, Basu, Gutnick, Wei, Shlevkov and Schwarz. 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 | Neuroscience Heo, Keunjung Basu, Himanish Gutnick, Amos Wei, Wei Shlevkov, Evgeny Schwarz, Thomas L. Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria |
title | Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria |
title_full | Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria |
title_fullStr | Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria |
title_full_unstemmed | Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria |
title_short | Serine/Threonine Protein Phosphatase 2A Regulates the Transport of Axonal Mitochondria |
title_sort | serine/threonine protein phosphatase 2a regulates the transport of axonal mitochondria |
topic | Neuroscience |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8973303/ https://www.ncbi.nlm.nih.gov/pubmed/35370563 http://dx.doi.org/10.3389/fncel.2022.852245 |
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