APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility

Understanding where in the cytoplasm mRNAs are translated is increasingly recognized as being as important as knowing the timing and level of protein expression. mRNAs are localized via active motor-driven transport along microtubules (MTs) but the underlying essential factors and dynamic interactio...

Descripción completa

Detalles Bibliográficos
Autores: Baumann, Sebastian, Grawenhoff, Julia, Rodrigues, Elsa C., Speroni, Silvia, Gili, Maria, Komissarov, Artem, 1992-, Maurer, Sebastian
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2022
País:España
Institución:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
Repositorio:Recercat. Dipósit de la Recerca de Catalunya
OAI Identifier:oai:recercat.cat:10230/55905
Acceso en línea:http://hdl.handle.net/10230/55905
http://dx.doi.org/10.1073/pnas.2211536119
Access Level:acceso abierto
Palabra clave:End binding proteins
Kinesin
mRNA transport
Microtubule cytoskeleton
id ES_c60520b954fb2e4aeb220dd40d55e836
oai_identifier_str oai:recercat.cat:10230/55905
network_acronym_str ES
network_name_str España
repository_id_str
spelling APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motilityBaumann, SebastianGrawenhoff, JuliaRodrigues, Elsa C.Speroni, SilviaGili, MariaKomissarov, Artem, 1992-Maurer, SebastianEnd binding proteinsKinesinmRNA transportMicrotubule cytoskeletonUnderstanding where in the cytoplasm mRNAs are translated is increasingly recognized as being as important as knowing the timing and level of protein expression. mRNAs are localized via active motor-driven transport along microtubules (MTs) but the underlying essential factors and dynamic interactions are largely unknown. Using biochemical in vitro reconstitutions with purified mammalian proteins, multicolor TIRF-microscopy, and interaction kinetics measurements, we show that adenomatous polyposis coli (APC) enables kinesin-1- and kinesin-2-based mRNA transport, and that APC is an ideal adaptor for long-range mRNA transport as it forms highly stable complexes with 3'UTR fragments of several neuronal mRNAs (APC-RNPs). The kinesin-1 KIF5A binds and transports several neuronal mRNP components such as FMRP, PURα and mRNA fragments weakly, whereas the transport frequency of the mRNA fragments is significantly increased by APC. APC-RNP-motor complexes can assemble on MTs, generating highly processive mRNA transport events. We further find that end-binding protein 1 (EB1) recruits APC-RNPs to dynamically growing MT ends and APC-RNPs track shrinking MTs, producing MT minus-end-directed RNA motility due to the high dwell times of APC on MTs. Our findings establish APC as a versatile mRNA-kinesin adaptor and a key factor for the assembly and bidirectional movement of neuronal transport mRNPs.This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) [BFU2017-85361-P], [PID2020-114870GB-I00], [BFU2015-62550-ERC], the Ministerio de Ciencia, Innovación y Universidades and Fondo Social Europeo (FSE) [PRE2018-084501], Juan de la Cierva-Incorporación Program [IJCI-2015-25994], the Human Frontiers in Science Program (HFSP) [RGY0083/2016], and the European Research Council (ERC) [H2020-MSCA-IF-2014-659271.]. We further acknowledge the support of the Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa’ [SEV-2012-0208].National Academy of Sciences202320232022info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfapplication/pdfhttp://hdl.handle.net/10230/55905http://dx.doi.org/10.1073/pnas.2211536119reponame:Recercat. Dipósit de la Recerca de Catalunyainstname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)InglésProc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2211536119info:eu-repo/grantAgreement/EC/H2020/659271info:eu-repo/grantAgreement/ES/2PE/BFU2017-85361-Pinfo:eu-repo/grantAgreement/ES/2PE/PID2020-114870GB-I00info:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERCinfo:eu-repo/grantAgreement/ES/2PE/PRE2018-084501© 2022 the Author(s). Published by PNAS. This open access article is distributed under Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND).https://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessoai:recercat.cat:10230/559052026-05-29T05:05:01Z
dc.title.none.fl_str_mv APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
title APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
spellingShingle APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
Baumann, Sebastian
End binding proteins
Kinesin
mRNA transport
Microtubule cytoskeleton
title_short APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
title_full APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
title_fullStr APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
title_full_unstemmed APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
title_sort APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
dc.creator.none.fl_str_mv Baumann, Sebastian
Grawenhoff, Julia
Rodrigues, Elsa C.
Speroni, Silvia
Gili, Maria
Komissarov, Artem, 1992-
Maurer, Sebastian
author Baumann, Sebastian
author_facet Baumann, Sebastian
Grawenhoff, Julia
Rodrigues, Elsa C.
Speroni, Silvia
Gili, Maria
Komissarov, Artem, 1992-
Maurer, Sebastian
author_role author
author2 Grawenhoff, Julia
Rodrigues, Elsa C.
Speroni, Silvia
Gili, Maria
Komissarov, Artem, 1992-
Maurer, Sebastian
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv End binding proteins
Kinesin
mRNA transport
Microtubule cytoskeleton
topic End binding proteins
Kinesin
mRNA transport
Microtubule cytoskeleton
description Understanding where in the cytoplasm mRNAs are translated is increasingly recognized as being as important as knowing the timing and level of protein expression. mRNAs are localized via active motor-driven transport along microtubules (MTs) but the underlying essential factors and dynamic interactions are largely unknown. Using biochemical in vitro reconstitutions with purified mammalian proteins, multicolor TIRF-microscopy, and interaction kinetics measurements, we show that adenomatous polyposis coli (APC) enables kinesin-1- and kinesin-2-based mRNA transport, and that APC is an ideal adaptor for long-range mRNA transport as it forms highly stable complexes with 3'UTR fragments of several neuronal mRNAs (APC-RNPs). The kinesin-1 KIF5A binds and transports several neuronal mRNP components such as FMRP, PURα and mRNA fragments weakly, whereas the transport frequency of the mRNA fragments is significantly increased by APC. APC-RNP-motor complexes can assemble on MTs, generating highly processive mRNA transport events. We further find that end-binding protein 1 (EB1) recruits APC-RNPs to dynamically growing MT ends and APC-RNPs track shrinking MTs, producing MT minus-end-directed RNA motility due to the high dwell times of APC on MTs. Our findings establish APC as a versatile mRNA-kinesin adaptor and a key factor for the assembly and bidirectional movement of neuronal transport mRNPs.
publishDate 2022
dc.date.none.fl_str_mv 2022
2023
2023
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://hdl.handle.net/10230/55905
http://dx.doi.org/10.1073/pnas.2211536119
url http://hdl.handle.net/10230/55905
http://dx.doi.org/10.1073/pnas.2211536119
dc.language.none.fl_str_mv Inglés
language_invalid_str_mv Inglés
dc.relation.none.fl_str_mv Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2211536119
info:eu-repo/grantAgreement/EC/H2020/659271
info:eu-repo/grantAgreement/ES/2PE/BFU2017-85361-P
info:eu-repo/grantAgreement/ES/2PE/PID2020-114870GB-I00
info:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERC
info:eu-repo/grantAgreement/ES/2PE/PRE2018-084501
dc.rights.none.fl_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by-nc-nd/4.0/
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
application/pdf
dc.publisher.none.fl_str_mv National Academy of Sciences
publisher.none.fl_str_mv National Academy of Sciences
dc.source.none.fl_str_mv reponame:Recercat. Dipósit de la Recerca de Catalunya
instname:Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
instname_str Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya)
reponame_str Recercat. Dipósit de la Recerca de Catalunya
collection Recercat. Dipósit de la Recerca de Catalunya
repository.name.fl_str_mv
repository.mail.fl_str_mv
_version_ 1869419037752033280
score 15,812429

Similares en LA Referencia