A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs

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  • dc.contributor.author Baumann, Sebastian
  • dc.contributor.author Komissarov, Artem, 1992-
  • dc.contributor.author Gili, Maria
  • dc.contributor.author Ruprecht, Verena
  • dc.contributor.author Wieser, Stefan
  • dc.contributor.author Maurer, Sebastian
  • dc.date.accessioned 2020-05-12T07:22:38Z
  • dc.date.available 2020-05-12T07:22:38Z
  • dc.date.issued 2020
  • dc.description.abstract Through the asymmetric distribution of messenger RNAs (mRNAs), cells spatially regulate gene expression to create cytoplasmic domains with specialized functions. In neurons, mRNA localization is required for essential processes such as cell polarization, migration, and synaptic plasticity underlying long-term memory formation. The essential components driving cytoplasmic mRNA transport in neurons and mammalian cells are not known. We report the first reconstitution of a mammalian mRNA transport system revealing that the tumor suppressor adenomatous polyposis coli (APC) forms stable complexes with the axonally localized β-actin and β2B-tubulin mRNAs, which are linked to a kinesin-2 via the cargo adaptor KAP3. APC activates kinesin-2, and both proteins are sufficient to drive specific transport of defined mRNA packages. Guanine-rich sequences located in 3'UTRs of axonal mRNAs increase transport efficiency and balance the access of different mRNAs to the transport system. Our findings reveal a minimal set of proteins sufficient to transport mammalian mRNAs.
  • dc.description.sponsorship This work was funded by the Spanish Ministry of Economy and Competitiveness (MINECO) (BFU2017-85361-P, BFU2014-54278-P, and BFU2015-62550-ERC), 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). V.R. acknowledges support from the Spanish Ministry of Economy and Competitiveness through the Program “Centro de Excelencia Severo Ochoa 2013–2017,” the CERCA Programme/Generalitat de Catalunya, MINECO’s Plan Nacional (BFU2017-86296-P). S.W. acknowledges support from the Spanish Ministry of Economy and Competitiveness through the “Severo Ochoa” program for Centres of Excellence in R&D (SEV-2015-0522), from Fundació Privada Cellex, and from Generalitat de Catalunya through the CERCA program. We further acknowledge support of the Spanish Ministry of Economy and Competitiveness (MEIC) to the EMBL partnership, “Centro de Excelencia Severo Ochoa” (SEV-2012-0208) and the CERCA Programme/Generalitat de Catalunya
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Baumann S, Komissarov A, Gili M, Ruprecht V, Wieser S, Maurer SP. A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs. Sci Adv. 2020 Mar 13; 6(11): eaaz1588. DOI: 10.1126/sciadv.aaz1588
  • dc.identifier.doi http://dx.doi.org/10.1126/sciadv.aaz1588
  • dc.identifier.issn 2375-2548
  • dc.identifier.uri http://hdl.handle.net/10230/44497
  • dc.language.iso eng
  • dc.publisher American Association for the Advancement of Science (AAAS)
  • dc.relation.ispartof Science Advances. 2020 Mar 13;6(11):eaaz1588
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/659271
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2014-54278-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERC
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/ BFU2017-85361-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/ BFU2017-86296-P
  • dc.rights © 2020 by Sebastian Baumann et al., some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC)
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri http://creativecommons.org/licenses/by-nc/4.0/
  • dc.subject.other RNA missatger
  • dc.subject.other Genètica
  • dc.subject.other Genòmica
  • dc.subject.other Tumors
  • dc.subject.other Proteïnes
  • dc.title A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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