Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation

Abstract Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved thr...

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Autores principales:	Eun-Ju Jin, Hyo Rim Ko, Inwoo Hwang, Byeong-Seong Kim, Jeong-Yun Choi, Kye Won Park, Sung-Woo Cho, Jee-Yin Ahn
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2018
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/538f9eccc6944d4ea7f95ddf10f2149e
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spelling	oai:doaj.org-article:538f9eccc6944d4ea7f95ddf10f2149e2021-12-02T15:08:41ZAkt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation10.1038/s41598-018-20755-w2045-2322https://doaj.org/article/538f9eccc6944d4ea7f95ddf10f2149e2018-02-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-20755-whttps://doaj.org/toc/2045-2322Abstract Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved threonine residue and modulate neurite outgrowth. Here we show that Akt binds to and phosphorylates a threonine 573 residue on radixin. Akt-mediated phosphorylation protects radixin from ubiquitin-dependent proteasomal degradation, thereby enhancing radixin protein stability, which permits proper neurite outgrowth and growth cone formation. Conversely, the inhibition of Akt kinase or disruption of Akt-dependent phosphorylation reduces the binding affinity of radixin to F-actin as well as lowers radixin protein levels, resulting in decreased neurite outgrowth and growth cone formation. Our findings suggest that Akt signaling regulates neurite outgrowth by stabilizing radixin interactions with F-actin, thus facilitating local F-actin dynamics.Eun-Ju JinHyo Rim KoInwoo HwangByeong-Seong KimJeong-Yun ChoiKye Won ParkSung-Woo ChoJee-Yin AhnNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-12 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Eun-Ju Jin Hyo Rim Ko Inwoo Hwang Byeong-Seong Kim Jeong-Yun Choi Kye Won Park Sung-Woo Cho Jee-Yin Ahn Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
description	Abstract Neurite growth is controlled by a complex molecular signaling network that regulates filamentous actin (F-actin) dynamics at the growth cone. The evolutionarily conserved ezrin, radixin, and moesin family of proteins tether F-actin to the cell membrane when phosphorylated at a conserved threonine residue and modulate neurite outgrowth. Here we show that Akt binds to and phosphorylates a threonine 573 residue on radixin. Akt-mediated phosphorylation protects radixin from ubiquitin-dependent proteasomal degradation, thereby enhancing radixin protein stability, which permits proper neurite outgrowth and growth cone formation. Conversely, the inhibition of Akt kinase or disruption of Akt-dependent phosphorylation reduces the binding affinity of radixin to F-actin as well as lowers radixin protein levels, resulting in decreased neurite outgrowth and growth cone formation. Our findings suggest that Akt signaling regulates neurite outgrowth by stabilizing radixin interactions with F-actin, thus facilitating local F-actin dynamics.
format	article
author	Eun-Ju Jin Hyo Rim Ko Inwoo Hwang Byeong-Seong Kim Jeong-Yun Choi Kye Won Park Sung-Woo Cho Jee-Yin Ahn
author_facet	Eun-Ju Jin Hyo Rim Ko Inwoo Hwang Byeong-Seong Kim Jeong-Yun Choi Kye Won Park Sung-Woo Cho Jee-Yin Ahn
author_sort	Eun-Ju Jin
title	Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
title_short	Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
title_full	Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
title_fullStr	Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
title_full_unstemmed	Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
title_sort	akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation
publisher	Nature Portfolio
publishDate	2018
url	https://doaj.org/article/538f9eccc6944d4ea7f95ddf10f2149e
work_keys_str_mv	AT eunjujin aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT hyorimko aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT inwoohwang aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT byeongseongkim aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT jeongyunchoi aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT kyewonpark aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT sungwoocho aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation AT jeeyinahn aktregulatesneuritegrowthbyphosphorylationdependentinhibitionofradixinproteasomaldegradation
_version_	1718388058595786752

Akt regulates neurite growth by phosphorylation-dependent inhibition of radixin proteasomal degradation

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