Molecular mechanism of dynein recruitment to kinetochores by the Rod-Zw10-Zwilch complex and Spindly
Autor(a) principal: | |
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Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , |
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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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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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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1817548057816858624 |