Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus

Abstract Doublecortin X (DCX), known to be essential for neuronal migration and cortical layering in the developing brain, is a 40 kDa microtubule (MT)-associated protein. DCX directly interacts with MTs via its two structured doublecortin (DC) domains, but the dynamics of this association and the p...

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Autores principales:	Maryam Moslehi, Dominic C. H. Ng, Marie A. Bogoyevitch
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/3169ed43ae2d47a9b8e4017edfd02153
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spelling	oai:doaj.org-article:3169ed43ae2d47a9b8e4017edfd021532021-12-02T11:52:31ZDynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus10.1038/s41598-017-05340-x2045-2322https://doaj.org/article/3169ed43ae2d47a9b8e4017edfd021532017-07-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-05340-xhttps://doaj.org/toc/2045-2322Abstract Doublecortin X (DCX), known to be essential for neuronal migration and cortical layering in the developing brain, is a 40 kDa microtubule (MT)-associated protein. DCX directly interacts with MTs via its two structured doublecortin (DC) domains, but the dynamics of this association and the possible regulatory roles played by the flanking unstructured regions remain poorly defined. Here, we employ quantitative fluorescence recovery after photobleaching (FRAP) protocols in living cells to reveal that DCX shows remarkably rapid and complete exchange within the MT network but that the removal of the C-terminal region significantly slows this exchange. We further probed how MT organization or external stimuli could additionally modulate DCX exchange dynamics. MT depolymerisation (nocodazole treatment) or stabilization (taxol treatment) further enhanced DCX exchange rates, however the exchange rates for the C-terminal truncated DCX protein were resistant to the impact of taxol-induced stabilization. Furthermore, in response to a hyperosmotic stress stimulus, DCX exchange dynamics were slowed, and again the C-terminal truncated DCX protein was resistant to the stimulus. Thus, the DCX dynamically associates with MTs in living cells and its C-terminal region plays important roles in the MT-DCX association.Maryam MoslehiDominic C. H. NgMarie A. BogoyevitchNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-11 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Maryam Moslehi Dominic C. H. Ng Marie A. Bogoyevitch Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus
description	Abstract Doublecortin X (DCX), known to be essential for neuronal migration and cortical layering in the developing brain, is a 40 kDa microtubule (MT)-associated protein. DCX directly interacts with MTs via its two structured doublecortin (DC) domains, but the dynamics of this association and the possible regulatory roles played by the flanking unstructured regions remain poorly defined. Here, we employ quantitative fluorescence recovery after photobleaching (FRAP) protocols in living cells to reveal that DCX shows remarkably rapid and complete exchange within the MT network but that the removal of the C-terminal region significantly slows this exchange. We further probed how MT organization or external stimuli could additionally modulate DCX exchange dynamics. MT depolymerisation (nocodazole treatment) or stabilization (taxol treatment) further enhanced DCX exchange rates, however the exchange rates for the C-terminal truncated DCX protein were resistant to the impact of taxol-induced stabilization. Furthermore, in response to a hyperosmotic stress stimulus, DCX exchange dynamics were slowed, and again the C-terminal truncated DCX protein was resistant to the stimulus. Thus, the DCX dynamically associates with MTs in living cells and its C-terminal region plays important roles in the MT-DCX association.
format	article
author	Maryam Moslehi Dominic C. H. Ng Marie A. Bogoyevitch
author_facet	Maryam Moslehi Dominic C. H. Ng Marie A. Bogoyevitch
author_sort	Maryam Moslehi
title	Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus
title_short	Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus
title_full	Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus
title_fullStr	Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus
title_full_unstemmed	Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus
title_sort	dynamic microtubule association of doublecortin x (dcx) is regulated by its c-terminus
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/3169ed43ae2d47a9b8e4017edfd02153
work_keys_str_mv	AT maryammoslehi dynamicmicrotubuleassociationofdoublecortinxdcxisregulatedbyitscterminus AT dominicchng dynamicmicrotubuleassociationofdoublecortinxdcxisregulatedbyitscterminus AT marieabogoyevitch dynamicmicrotubuleassociationofdoublecortinxdcxisregulatedbyitscterminus
_version_	1718394975335481344

Dynamic microtubule association of Doublecortin X (DCX) is regulated by its C-terminus

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