SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis

Abstract Forkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required fo...

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Autores principales:	Daniel L. Rocca, Kevin A. Wilkinson, Jeremy M. Henley
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/c1afe41fc37b48c8a2305781f35bd76b
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spelling	oai:doaj.org-article:c1afe41fc37b48c8a2305781f35bd76b2021-12-02T15:18:54ZSUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis10.1038/s41598-017-00707-62045-2322https://doaj.org/article/c1afe41fc37b48c8a2305781f35bd76b2017-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-00707-6https://doaj.org/toc/2045-2322Abstract Forkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co-repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly controlled by neuronal activity, in which synapse to nucleus signalling, mediated via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation. Knockdown of FOXP1 in cultured cortical neurons stunts dendritic outgrowth and this phenotype cannot be rescued by replacement with a non-SUMOylatable FOXP1-K670R mutant, indicating that SUMOylation of FOXP1 is essential for regulation of proper neuronal morphogenesis. These results suggest that activity-dependent SUMOylation of FOXP1 may be an important mediator of early cortical development and neuronal network formation in the brain.Daniel L. RoccaKevin A. WilkinsonJeremy M. HenleyNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Daniel L. Rocca Kevin A. Wilkinson Jeremy M. Henley SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
description	Abstract Forkhead Box P (FOXP) transcriptional repressors play a major role in brain development and their dysfunction leads to human cognitive disorders. However, little is known about how the activity of these proteins is regulated. Here, we show that FOXP1 SUMOylation at lysine 670 is required for recruiting the co-repressor CtBP1 and transcriptional repression. FOXP1 SUMOylation is tightly controlled by neuronal activity, in which synapse to nucleus signalling, mediated via NMDAR and L-type calcium channels, results in rapid FOXP1 deSUMOylation. Knockdown of FOXP1 in cultured cortical neurons stunts dendritic outgrowth and this phenotype cannot be rescued by replacement with a non-SUMOylatable FOXP1-K670R mutant, indicating that SUMOylation of FOXP1 is essential for regulation of proper neuronal morphogenesis. These results suggest that activity-dependent SUMOylation of FOXP1 may be an important mediator of early cortical development and neuronal network formation in the brain.
format	article
author	Daniel L. Rocca Kevin A. Wilkinson Jeremy M. Henley
author_facet	Daniel L. Rocca Kevin A. Wilkinson Jeremy M. Henley
author_sort	Daniel L. Rocca
title	SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
title_short	SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
title_full	SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
title_fullStr	SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
title_full_unstemmed	SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis
title_sort	sumoylation of foxp1 regulates transcriptional repression via ctbp1 to drive dendritic morphogenesis
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/c1afe41fc37b48c8a2305781f35bd76b
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SUMOylation of FOXP1 regulates transcriptional repression via CtBP1 to drive dendritic morphogenesis

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