دورية أكاديمية

Self-Assembly of the RZZ Complex into Filaments Drives Kinetochore Expansion in the Absence of Microtubule Attachment.

التفاصيل البيبلوغرافية
العنوان: Self-Assembly of the RZZ Complex into Filaments Drives Kinetochore Expansion in the Absence of Microtubule Attachment.
المؤلفون: Pereira C; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal., Reis RM; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal., Gama JB; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal., Celestino R; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal., Cheerambathur DK; Ludwig Institute for Cancer Research, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA., Carvalho AX; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal., Gassmann R; Instituto de Biologia Molecular e Celular (IBMC), Universidade do Porto, 4200-135 Porto, Portugal; Instituto de Investigação e Inovação em Saúde (i3S), Universidade do Porto, 4200-135 Porto, Portugal. Electronic address: rgassmann@ibmc.up.pt.
المصدر: Current biology : CB [Curr Biol] 2018 Nov 05; Vol. 28 (21), pp. 3408-3421.e8. Date of Electronic Publication: 2018 Oct 25.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Cell Press Country of Publication: England NLM ID: 9107782 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0445 (Electronic) Linking ISSN: 09609822 NLM ISO Abbreviation: Curr Biol Subsets: MEDLINE
أسماء مطبوعة: Publication: Cambridge, MA : Cell Press
Original Publication: London, UK : Current Biology Ltd., c1991-
مواضيع طبية MeSH: Caenorhabditis elegans/*metabolism , Kinetochores/*metabolism , Microtubules/*metabolism, Animals ; Caenorhabditis elegans/embryology ; Cell Cycle Proteins/genetics ; Cell Cycle Proteins/metabolism ; Dyneins/metabolism ; Humans ; Mad2 Proteins/genetics ; Mad2 Proteins/metabolism ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism
مستخلص: The kinetochore is a dynamic multi-protein assembly that forms on each sister chromatid and interacts with microtubules of the mitotic spindle to drive chromosome segregation. In animals, kinetochores without attached microtubules expand their outermost layer into crescent and ring shapes to promote microtubule capture and spindle assembly checkpoint (SAC) signaling. Kinetochore expansion is an example of protein co-polymerization, but the mechanism is not understood. Here, we present evidence that kinetochore expansion is driven by oligomerization of the Rod-Zw10-Zwilch (RZZ) complex, an outer kinetochore component that recruits the motor dynein and the SAC proteins Mad1-Mad2. Depletion of ROD in human cells suppresses kinetochore expansion, as does depletion of Spindly, the adaptor that connects RZZ to dynein, although dynein itself is dispensable. Expansion is also suppressed by mutating ZWILCH residues implicated in Spindly binding. Conversely, supplying cells with excess ROD facilitates kinetochore expansion under otherwise prohibitive conditions. Using the C. elegans early embryo, we demonstrate that ROD-1 has a concentration-dependent propensity for oligomerizing into micrometer-scale filaments, and we identify the ROD-1 β-propeller as a key regulator of self-assembly. Finally, we show that a minimal ROD-1-Zw10 complex efficiently oligomerizes into filaments in vitro. Our results suggest that RZZ's capacity for oligomerization is harnessed by kinetochores to assemble the expanded outermost domain, in which RZZ filaments serve as recruitment platforms for SAC components and microtubule-binding proteins. Thus, we propose that reversible RZZ self-assembly into filaments underlies the adaptive change in kinetochore size that contributes to chromosome segregation fidelity.
(Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.)
التعليقات: Comment in: Curr Biol. 2018 Nov 5;28(21):R1250-R1252. (PMID: 30399347)
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فهرسة مساهمة: Keywords: RZZ complex; dynein; fibrous corona; kinetochore; mitosis; spindle assembly checkpoint; spindly
المشرفين على المادة: 0 (Cell Cycle Proteins)
0 (MAD1L1 protein, human)
0 (MAD2L1 protein, human)
0 (Mad2 Proteins)
0 (Nuclear Proteins)
EC 3.6.4.2 (Dyneins)
تواريخ الأحداث: Date Created: 20181113 Date Completed: 20191025 Latest Revision: 20231004
رمز التحديث: 20231004
مُعرف محوري في PubMed: PMC6224608
DOI: 10.1016/j.cub.2018.08.056
PMID: 30415699
قاعدة البيانات: MEDLINE
الوصف
تدمد:1879-0445
DOI:10.1016/j.cub.2018.08.056