Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly

Detalhes bibliográficos
Autor(a) principal: Gama, JB
Data de Publicação: 2017
Outros Autores: Pereira, C, Simões, PA, Celestino, R, Reis, RM, Barbosa, DJ, Pires, HR, Carvalho, C, Amorim, J, Carvalho, AX, Cheerambathur, DK, Gassmann, R
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10216/110360
Resumo: The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal beta-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod beta-propeller-Zwilch complex in vitro. Spindly's N-terminal coiled-coil uses distinct motifs to bind dynein light intermediate chain and the pointed-end complex of dynactin. Mutations in these motifs inhibit assembly of a dynein-dynactin-Spindly complex, and a null mutant of the dynactin pointed-end subunit p27 prevents kinetochore recruitment of dynein-dynactin without affecting other mitotic functions of the motor. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.
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spelling Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and SpindlyAnimalsCaenorhabditis elegans/metabolismCaenorhabditis elegans/physiologyCarrier Proteins/metabolismCell Cycle Proteins/metabolismCell Line, TumorChromosomal Proteins Non-Histone/metabolismChromosome Segregation/physiologyDynactin Complex/metabolismDyneins/metabolismHeLa CellsHumansKinetochores/metabolismKinetochores/physiologyMicrotubule-Associated Proteins/metabolismMicrotubules/metabolismMicrotubules/physiologyMitosis/physiologySpindle Apparatus/metabolismSpindle Apparatus/physiologyThe molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal beta-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod beta-propeller-Zwilch complex in vitro. Spindly's N-terminal coiled-coil uses distinct motifs to bind dynein light intermediate chain and the pointed-end complex of dynactin. Mutations in these motifs inhibit assembly of a dynein-dynactin-Spindly complex, and a null mutant of the dynactin pointed-end subunit p27 prevents kinetochore recruitment of dynein-dynactin without affecting other mitotic functions of the motor. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.Rockefeller University Press20172017-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfapplication/pdfapplication/octet-streamapplication/octet-streamapplication/octet-streamapplication/octet-streamapplication/ziphttp://hdl.handle.net/10216/110360eng0021-952510.1083/jcb.201610108Gama, JBPereira, CSimões, PACelestino, RReis, RMBarbosa, DJPires, HRCarvalho, CAmorim, JCarvalho, AXCheerambathur, DKGassmann, Rinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-09-27T08:51:47Zoai:repositorio-aberto.up.pt:10216/110360Portal AgregadorONGhttps://www.rcaap.pt/oai/openairemluisa.alvim@gmail.comopendoar:71602024-09-27T08:51:47Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
title Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
spellingShingle Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
Gama, JB
Animals
Caenorhabditis elegans/metabolism
Caenorhabditis elegans/physiology
Carrier Proteins/metabolism
Cell Cycle Proteins/metabolism
Cell Line, Tumor
Chromosomal Proteins Non-Histone/metabolism
Chromosome Segregation/physiology
Dynactin Complex/metabolism
Dyneins/metabolism
HeLa Cells
Humans
Kinetochores/metabolism
Kinetochores/physiology
Microtubule-Associated Proteins/metabolism
Microtubules/metabolism
Microtubules/physiology
Mitosis/physiology
Spindle Apparatus/metabolism
Spindle Apparatus/physiology
title_short Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
title_full Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
title_fullStr Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
title_full_unstemmed Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
title_sort Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
author Gama, JB
author_facet Gama, JB
Pereira, C
Simões, PA
Celestino, R
Reis, RM
Barbosa, DJ
Pires, HR
Carvalho, C
Amorim, J
Carvalho, AX
Cheerambathur, DK
Gassmann, R
author_role author
author2 Pereira, C
Simões, PA
Celestino, R
Reis, RM
Barbosa, DJ
Pires, HR
Carvalho, C
Amorim, J
Carvalho, AX
Cheerambathur, DK
Gassmann, R
author2_role author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Gama, JB
Pereira, C
Simões, PA
Celestino, R
Reis, RM
Barbosa, DJ
Pires, HR
Carvalho, C
Amorim, J
Carvalho, AX
Cheerambathur, DK
Gassmann, R
dc.subject.por.fl_str_mv Animals
Caenorhabditis elegans/metabolism
Caenorhabditis elegans/physiology
Carrier Proteins/metabolism
Cell Cycle Proteins/metabolism
Cell Line, Tumor
Chromosomal Proteins Non-Histone/metabolism
Chromosome Segregation/physiology
Dynactin Complex/metabolism
Dyneins/metabolism
HeLa Cells
Humans
Kinetochores/metabolism
Kinetochores/physiology
Microtubule-Associated Proteins/metabolism
Microtubules/metabolism
Microtubules/physiology
Mitosis/physiology
Spindle Apparatus/metabolism
Spindle Apparatus/physiology
topic Animals
Caenorhabditis elegans/metabolism
Caenorhabditis elegans/physiology
Carrier Proteins/metabolism
Cell Cycle Proteins/metabolism
Cell Line, Tumor
Chromosomal Proteins Non-Histone/metabolism
Chromosome Segregation/physiology
Dynactin Complex/metabolism
Dyneins/metabolism
HeLa Cells
Humans
Kinetochores/metabolism
Kinetochores/physiology
Microtubule-Associated Proteins/metabolism
Microtubules/metabolism
Microtubules/physiology
Mitosis/physiology
Spindle Apparatus/metabolism
Spindle Apparatus/physiology
description The molecular motor dynein concentrates at the kinetochore region of mitotic chromosomes in animals to accelerate spindle microtubule capture and to control spindle checkpoint signaling. In this study, we describe the molecular mechanism used by the Rod-Zw10-Zwilch complex and the adaptor Spindly to recruit dynein to kinetochores in Caenorhabditis elegans embryos and human cells. We show that Rod's N-terminal beta-propeller and the associated Zwilch subunit bind Spindly's C-terminal domain, and we identify a specific Zwilch mutant that abrogates Spindly and dynein recruitment in vivo and Spindly binding to a Rod beta-propeller-Zwilch complex in vitro. Spindly's N-terminal coiled-coil uses distinct motifs to bind dynein light intermediate chain and the pointed-end complex of dynactin. Mutations in these motifs inhibit assembly of a dynein-dynactin-Spindly complex, and a null mutant of the dynactin pointed-end subunit p27 prevents kinetochore recruitment of dynein-dynactin without affecting other mitotic functions of the motor. Conservation of Spindly-like motifs in adaptors involved in intracellular transport suggests a common mechanism for linking dynein to cargo.
publishDate 2017
dc.date.none.fl_str_mv 2017
2017-01-01T00:00:00Z
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10216/110360
url http://hdl.handle.net/10216/110360
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 0021-9525
10.1083/jcb.201610108
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
application/octet-stream
application/octet-stream
application/octet-stream
application/octet-stream
application/zip
dc.publisher.none.fl_str_mv Rockefeller University Press
publisher.none.fl_str_mv Rockefeller University Press
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron:RCAAP
instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
institution RCAAP
reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
repository.mail.fl_str_mv mluisa.alvim@gmail.com
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