The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation

Abstract Cytoplasmic dynein 1 is a multi-protein intracellular motor essential for mediating several mitotic functions, including the establishment of proper spindle orientation. The functional relevance and mechanistic distinctions between two discrete dynein subpopulations distinguished only by Li...

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Autores principales:	Sagar Mahale, Megha Kumar, Amit Sharma, Aswini Babu, Shashi Ranjan, Chetana Sachidanandan, Sivaram V. S. Mylavarapu
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2016
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f8dcadbb665b4656a8290ae5ae5ba831
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spelling	oai:doaj.org-article:f8dcadbb665b4656a8290ae5ae5ba8312021-12-02T15:06:06ZThe Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation10.1038/s41598-016-0030-32045-2322https://doaj.org/article/f8dcadbb665b4656a8290ae5ae5ba8312016-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-016-0030-3https://doaj.org/toc/2045-2322Abstract Cytoplasmic dynein 1 is a multi-protein intracellular motor essential for mediating several mitotic functions, including the establishment of proper spindle orientation. The functional relevance and mechanistic distinctions between two discrete dynein subpopulations distinguished only by Light Intermediate Chain (LIC) homologues, LIC1 and LIC2 is unknown during mitosis. Here, we identify LIC2-dynein as the major mediator of proper spindle orientation and uncover its underlying molecular mechanism. Cortically localized dynein, essential for maintaining correct spindle orientation, consists majorly of LIC2-dynein, which interacts with cortical 14-3-3 ε- ζ and Par3, conserved proteins required for orienting the spindle. LIC2-dynein is also responsible for the majority of dynein-mediated asymmetric poleward transport of NuMA, helping focus microtubule minus ends. In addition, LIC2-dynein dominates in equatorially aligning chromosomes at metaphase and in regulating mitotic spindle length. Key mitotic functions of LIC2 were remarkably conserved in and essential for early embryonic divisions and development in zebrafish. Thus LIC2-dynein exclusively engages with two major cortical pathways to govern spindle orientation. Overall, we identify a novel selectivity of molecular interactions between the two LICs in mitosis as the underlying basis for their uneven distribution of labour in ensuring proper spindle orientation.Sagar MahaleMegha KumarAmit SharmaAswini BabuShashi RanjanChetana SachidanandanSivaram V. S. MylavarapuNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 6, Iss 1, Pp 1-16 (2016)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sagar Mahale Megha Kumar Amit Sharma Aswini Babu Shashi Ranjan Chetana Sachidanandan Sivaram V. S. Mylavarapu The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation
description	Abstract Cytoplasmic dynein 1 is a multi-protein intracellular motor essential for mediating several mitotic functions, including the establishment of proper spindle orientation. The functional relevance and mechanistic distinctions between two discrete dynein subpopulations distinguished only by Light Intermediate Chain (LIC) homologues, LIC1 and LIC2 is unknown during mitosis. Here, we identify LIC2-dynein as the major mediator of proper spindle orientation and uncover its underlying molecular mechanism. Cortically localized dynein, essential for maintaining correct spindle orientation, consists majorly of LIC2-dynein, which interacts with cortical 14-3-3 ε- ζ and Par3, conserved proteins required for orienting the spindle. LIC2-dynein is also responsible for the majority of dynein-mediated asymmetric poleward transport of NuMA, helping focus microtubule minus ends. In addition, LIC2-dynein dominates in equatorially aligning chromosomes at metaphase and in regulating mitotic spindle length. Key mitotic functions of LIC2 were remarkably conserved in and essential for early embryonic divisions and development in zebrafish. Thus LIC2-dynein exclusively engages with two major cortical pathways to govern spindle orientation. Overall, we identify a novel selectivity of molecular interactions between the two LICs in mitosis as the underlying basis for their uneven distribution of labour in ensuring proper spindle orientation.
format	article
author	Sagar Mahale Megha Kumar Amit Sharma Aswini Babu Shashi Ranjan Chetana Sachidanandan Sivaram V. S. Mylavarapu
author_facet	Sagar Mahale Megha Kumar Amit Sharma Aswini Babu Shashi Ranjan Chetana Sachidanandan Sivaram V. S. Mylavarapu
author_sort	Sagar Mahale
title	The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation
title_short	The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation
title_full	The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation
title_fullStr	The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation
title_full_unstemmed	The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation
title_sort	light intermediate chain 2 subpopulation of dynein regulates mitotic spindle orientation
publisher	Nature Portfolio
publishDate	2016
url	https://doaj.org/article/f8dcadbb665b4656a8290ae5ae5ba831
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The Light Intermediate Chain 2 Subpopulation of Dynein Regulates Mitotic Spindle Orientation

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