Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability

Abstract Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are...

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Autores principales:	L.-P. Croteau, T.-J. Kao, A. Kania
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2019
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/464d9c8445eb451692641b02dcdd074e
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spelling	oai:doaj.org-article:464d9c8445eb451692641b02dcdd074e2021-12-02T15:08:07ZEphrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability10.1038/s41598-019-48519-02045-2322https://doaj.org/article/464d9c8445eb451692641b02dcdd074e2019-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-019-48519-0https://doaj.org/toc/2045-2322Abstract Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.L.-P. CroteauT.-J. KaoA. KaniaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 9, Iss 1, Pp 1-17 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q L.-P. Croteau T.-J. Kao A. Kania Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
description	Abstract Axonal growth cones are guided by molecular cues in the extracellular environment. The mechanisms of combinatorial integration of guidance signals at the growth cone cell membrane are still being unravelled. Limb-innervating axons of vertebrate spinal lateral motor column (LMC) neurons are attracted to netrin-1 via its receptor, Neogenin, and are repelled from ephrin-A5 through its receptor EphA4. The presence of both cues elicits synergistic guidance of LMC axons, but the mechanism of this effect remains unknown. Using fluorescence immunohistochemistry, we show that ephrin-A5 increases LMC growth cone Neogenin protein levels and netrin-1 binding. This effect is enhanced by overexpressing EphA4 and is inhibited by blocking ephrin-A5-EphA4 binding. These effects have a functional consequence on LMC growth cone responses since bath addition of ephrin-A5 increases the responsiveness of LMC axons to netrin-1. Surprisingly, the overexpression of EphA4 lacking its cytoplasmic tail, also enhances Neogenin levels at the growth cone and potentiates LMC axon preference for growth on netrin-1. Since netrins and ephrins participate in a wide variety of biological processes, the enhancement of netrin-1 signalling by ephrins may have broad implications.
format	article
author	L.-P. Croteau T.-J. Kao A. Kania
author_facet	L.-P. Croteau T.-J. Kao A. Kania
author_sort	L.-P. Croteau
title	Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
title_short	Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
title_full	Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
title_fullStr	Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
title_full_unstemmed	Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability
title_sort	ephrin-a5 potentiates netrin-1 axon guidance by enhancing neogenin availability
publisher	Nature Portfolio
publishDate	2019
url	https://doaj.org/article/464d9c8445eb451692641b02dcdd074e
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Ephrin-A5 potentiates netrin-1 axon guidance by enhancing Neogenin availability

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