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The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis

Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical r...

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Autores principales: Cheerambathur, Dhanya K., Prevo, Bram, Chow, Tiffany-Lynn, Hattersley, Neil, Wang, Shaohe, Zhao, Zhiling, Kim, Taekyung, Gerson-Gurwitz, Adina, Oegema, Karen, Green, Rebecca, Desai, Arshad
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Cell Press 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436928/
https://www.ncbi.nlm.nih.gov/pubmed/30827898
http://dx.doi.org/10.1016/j.devcel.2019.02.002
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author Cheerambathur, Dhanya K.
Prevo, Bram
Chow, Tiffany-Lynn
Hattersley, Neil
Wang, Shaohe
Zhao, Zhiling
Kim, Taekyung
Gerson-Gurwitz, Adina
Oegema, Karen
Green, Rebecca
Desai, Arshad
author_facet Cheerambathur, Dhanya K.
Prevo, Bram
Chow, Tiffany-Lynn
Hattersley, Neil
Wang, Shaohe
Zhao, Zhiling
Kim, Taekyung
Gerson-Gurwitz, Adina
Oegema, Karen
Green, Rebecca
Desai, Arshad
author_sort Cheerambathur, Dhanya K.
collection PubMed
description Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis.
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spelling pubmed-64369282019-04-10 The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis Cheerambathur, Dhanya K. Prevo, Bram Chow, Tiffany-Lynn Hattersley, Neil Wang, Shaohe Zhao, Zhiling Kim, Taekyung Gerson-Gurwitz, Adina Oegema, Karen Green, Rebecca Desai, Arshad Dev Cell Article Dynamic coupling of microtubule ends to kinetochores, built on the centromeres of chromosomes, directs chromosome segregation during cell division. Here, we report that the evolutionarily ancient kinetochore-microtubule coupling machine, the KMN (Knl1/Mis12/Ndc80-complex) network, plays a critical role in neuronal morphogenesis. We show that the KMN network concentrates in microtubule-rich dendrites of developing sensory neurons that collectively extend in a multicellular morphogenetic event that occurs during C. elegans embryogenesis. Post-mitotic degradation of KMN components in sensory neurons disrupts dendritic extension, leading to patterning and functional defects in the sensory nervous system. Structure-guided mutations revealed that the molecular interface that couples kinetochores to spindle microtubules also functions in neuronal development. These results identify a cell-division-independent function for the chromosome-segregation machinery and define a microtubule-coupling-dependent event in sensory nervous system morphogenesis. Cell Press 2019-03-25 /pmc/articles/PMC6436928/ /pubmed/30827898 http://dx.doi.org/10.1016/j.devcel.2019.02.002 Text en © 2019 The Authors http://creativecommons.org/licenses/by/4.0/ This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Cheerambathur, Dhanya K.
Prevo, Bram
Chow, Tiffany-Lynn
Hattersley, Neil
Wang, Shaohe
Zhao, Zhiling
Kim, Taekyung
Gerson-Gurwitz, Adina
Oegema, Karen
Green, Rebecca
Desai, Arshad
The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis
title The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis
title_full The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis
title_fullStr The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis
title_full_unstemmed The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis
title_short The Kinetochore-Microtubule Coupling Machinery Is Repurposed in Sensory Nervous System Morphogenesis
title_sort kinetochore-microtubule coupling machinery is repurposed in sensory nervous system morphogenesis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6436928/
https://www.ncbi.nlm.nih.gov/pubmed/30827898
http://dx.doi.org/10.1016/j.devcel.2019.02.002
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