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

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  • dc.contributor.author Baumann, Sebastian
  • dc.contributor.author Grawenhoff, Julia
  • dc.contributor.author Rodrigues, Elsa C.
  • dc.contributor.author Speroni, Silvia
  • dc.contributor.author Gili, Maria
  • dc.contributor.author Komissarov, Artem, 1992-
  • dc.contributor.author Maurer, Sebastian
  • dc.date.accessioned 2023-02-24T07:00:57Z
  • dc.date.available 2023-02-24T07:00:57Z
  • dc.date.issued 2022
  • dc.description.abstract 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.
  • dc.description.sponsorship 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].
  • dc.format.mimetype application/pdf
  • dc.identifier.citation Baumann SJ, Grawenhoff J, Rodrigues EC, Speroni S, Gili M, Komissarov A, Maurer SP. APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility. Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2211536119. DOI: 10.1073/pnas.2211536119
  • dc.identifier.doi http://dx.doi.org/10.1073/pnas.2211536119
  • dc.identifier.issn 0027-8424
  • dc.identifier.uri http://hdl.handle.net/10230/55905
  • dc.language.iso eng
  • dc.publisher National Academy of Sciences
  • dc.relation.ispartof Proc Natl Acad Sci U S A. 2022 Dec 13;119(50):e2211536119
  • dc.relation.projectID info:eu-repo/grantAgreement/EC/H2020/659271
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-85361-P
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-114870GB-I00
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/1PE/BFU2015-62550-ERC
  • dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PRE2018-084501
  • dc.rights © 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).
  • dc.rights.accessRights info:eu-repo/semantics/openAccess
  • dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
  • dc.subject.keyword End binding proteins
  • dc.subject.keyword Kinesin
  • dc.subject.keyword mRNA transport
  • dc.subject.keyword Microtubule cytoskeleton
  • dc.title APC couples neuronal mRNAs to multiple kinesins, EB1, and shrinking microtubule ends for bidirectional mRNA motility
  • dc.type info:eu-repo/semantics/article
  • dc.type.version info:eu-repo/semantics/publishedVersion

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