NuMA recruits dynein activity to microtubule minus-ends at mitosis
To build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-e...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2017-11-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/29328 |
| _version_ | 1828381032539226112 |
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| author | Christina L Hueschen Samuel J Kenny Ke Xu Sophie Dumont |
| author_facet | Christina L Hueschen Samuel J Kenny Ke Xu Sophie Dumont |
| author_sort | Christina L Hueschen |
| collection | DOAJ |
| description | To build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-ends is not known. Here, we use quantitative imaging and laser ablation to show that NuMA targets dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to new minus-ends independently of dynein and more quickly than dynactin; both NuMA and dynactin display specific, steady-state binding at minus-ends. NuMA localization to minus-ends involves a C-terminal region outside NuMA’s canonical microtubule-binding domain and is independent of minus-end binders γ-TuRC, CAMSAP1, and KANSL1/3. Both NuMA’s minus-end-binding and dynein-dynactin-binding modules are required to rescue focused, bipolar spindle organization. Thus, NuMA may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein activity to minus-ends to cluster spindle microtubules into poles. |
| first_indexed | 2024-12-10T04:08:49Z |
| format | Article |
| id | doaj.art-179ad9d4922b4af5a9be2c8dfa5d5878 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T04:08:49Z |
| publishDate | 2017-11-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-179ad9d4922b4af5a9be2c8dfa5d58782022-12-22T02:02:47ZengeLife Sciences Publications LtdeLife2050-084X2017-11-01610.7554/eLife.29328NuMA recruits dynein activity to microtubule minus-ends at mitosisChristina L Hueschen0https://orcid.org/0000-0002-3437-2895Samuel J Kenny1Ke Xu2https://orcid.org/0000-0002-2788-194XSophie Dumont3https://orcid.org/0000-0002-8283-1523Department of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, United StatesDepartment of Chemistry, University of California, Berkeley, Berkeley, United StatesDepartment of Chemistry, University of California, Berkeley, Berkeley, United StatesDepartment of Cell and Tissue Biology, University of California, San Francisco, San Francisco, United States; Biomedical Sciences Graduate Program, University of California, San Francisco, San Francisco, United States; Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, United StatesTo build the spindle at mitosis, motors exert spatially regulated forces on microtubules. We know that dynein pulls on mammalian spindle microtubule minus-ends, and this localized activity at ends is predicted to allow dynein to cluster microtubules into poles. How dynein becomes enriched at minus-ends is not known. Here, we use quantitative imaging and laser ablation to show that NuMA targets dynactin to minus-ends, localizing dynein activity there. NuMA is recruited to new minus-ends independently of dynein and more quickly than dynactin; both NuMA and dynactin display specific, steady-state binding at minus-ends. NuMA localization to minus-ends involves a C-terminal region outside NuMA’s canonical microtubule-binding domain and is independent of minus-end binders γ-TuRC, CAMSAP1, and KANSL1/3. Both NuMA’s minus-end-binding and dynein-dynactin-binding modules are required to rescue focused, bipolar spindle organization. Thus, NuMA may serve as a mitosis-specific minus-end cargo adaptor, targeting dynein activity to minus-ends to cluster spindle microtubules into poles.https://elifesciences.org/articles/29328Potorous tridactylusmitosisspindlemicrotubuledyneinminus-end |
| spellingShingle | Christina L Hueschen Samuel J Kenny Ke Xu Sophie Dumont NuMA recruits dynein activity to microtubule minus-ends at mitosis eLife Potorous tridactylus mitosis spindle microtubule dynein minus-end |
| title | NuMA recruits dynein activity to microtubule minus-ends at mitosis |
| title_full | NuMA recruits dynein activity to microtubule minus-ends at mitosis |
| title_fullStr | NuMA recruits dynein activity to microtubule minus-ends at mitosis |
| title_full_unstemmed | NuMA recruits dynein activity to microtubule minus-ends at mitosis |
| title_short | NuMA recruits dynein activity to microtubule minus-ends at mitosis |
| title_sort | numa recruits dynein activity to microtubule minus ends at mitosis |
| topic | Potorous tridactylus mitosis spindle microtubule dynein minus-end |
| url | https://elifesciences.org/articles/29328 |
| work_keys_str_mv | AT christinalhueschen numarecruitsdyneinactivitytomicrotubuleminusendsatmitosis AT samueljkenny numarecruitsdyneinactivitytomicrotubuleminusendsatmitosis AT kexu numarecruitsdyneinactivitytomicrotubuleminusendsatmitosis AT sophiedumont numarecruitsdyneinactivitytomicrotubuleminusendsatmitosis |