High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching

Abstract Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation—a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative dise...

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Autores principales:	Sara M. Blazejewski, Sarah A. Bennison, Xiaonan Liu, Kazuhito Toyo-oka
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/30d842c26792468bb97dfa5ff0adfc28
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spelling	oai:doaj.org-article:30d842c26792468bb97dfa5ff0adfc282021-12-02T14:26:25ZHigh-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching10.1038/s41598-021-87521-32045-2322https://doaj.org/article/30d842c26792468bb97dfa5ff0adfc282021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-87521-3https://doaj.org/toc/2045-2322Abstract Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation—a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative disease, and seizures. Investigating the mechanisms underlying neurite formation will allow for identification of potential therapeutics. We used a kinase inhibitor library to screen 493 kinase inhibitors and observed that 45% impacted neuritogenesis in Neuro2a (N-2a) cells. Based on the screening, we further investigated the roles of Aurora kinases A, B, and C and Nuak kinases 1 and 2. The roles of Aurora and Nuak kinases have not been thoroughly studied in the nervous system. Inhibition or overexpression of Aurora and Nuak kinases in primary cortical neurons resulted in various neuromorphological defects, with Aurora A regulating neurite initiation, Aurora B and C regulating neurite initiation and elongation, all Aurora kinases regulating arborization, and all Nuak kinases regulating neurite initiation and elongation and arborization. Our high-throughput screening and analysis of Aurora and Nuak kinases revealed their functions and may contribute to the identification of therapeutics.Sara M. BlazejewskiSarah A. BennisonXiaonan LiuKazuhito Toyo-okaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-20 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sara M. Blazejewski Sarah A. Bennison Xiaonan Liu Kazuhito Toyo-oka High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
description	Abstract Kinases are essential regulators of a variety of cellular signaling processes, including neurite formation—a foundational step in neurodevelopment. Aberrant axonal sprouting and failed regeneration of injured axons are associated with conditions like traumatic injury, neurodegenerative disease, and seizures. Investigating the mechanisms underlying neurite formation will allow for identification of potential therapeutics. We used a kinase inhibitor library to screen 493 kinase inhibitors and observed that 45% impacted neuritogenesis in Neuro2a (N-2a) cells. Based on the screening, we further investigated the roles of Aurora kinases A, B, and C and Nuak kinases 1 and 2. The roles of Aurora and Nuak kinases have not been thoroughly studied in the nervous system. Inhibition or overexpression of Aurora and Nuak kinases in primary cortical neurons resulted in various neuromorphological defects, with Aurora A regulating neurite initiation, Aurora B and C regulating neurite initiation and elongation, all Aurora kinases regulating arborization, and all Nuak kinases regulating neurite initiation and elongation and arborization. Our high-throughput screening and analysis of Aurora and Nuak kinases revealed their functions and may contribute to the identification of therapeutics.
format	article
author	Sara M. Blazejewski Sarah A. Bennison Xiaonan Liu Kazuhito Toyo-oka
author_facet	Sara M. Blazejewski Sarah A. Bennison Xiaonan Liu Kazuhito Toyo-oka
author_sort	Sara M. Blazejewski
title	High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
title_short	High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
title_full	High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
title_fullStr	High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
title_full_unstemmed	High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching
title_sort	high-throughput kinase inhibitor screening reveals roles for aurora and nuak kinases in neurite initiation and dendritic branching
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/30d842c26792468bb97dfa5ff0adfc28
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High-throughput kinase inhibitor screening reveals roles for Aurora and Nuak kinases in neurite initiation and dendritic branching

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