A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs
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...
| Authors: | ; ; ; ; ; |
|---|---|
| Format: | Article |
| Status: | Published version |
| Publication date: | 2020 |
| Country: | España |
| Institution: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repository: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10230/44497 |
| Online Access: | http://hdl.handle.net/10230/44497 http://dx.doi.org/10.1126/sciadv.aaz1588 |
| Access Level: | Open access |
| Keyword: | RNA missatger Genètica Genòmica Tumors Proteïnes |
| _version_ | 1878739193189892096 |
|---|---|
| author | Baumann, Sebastian |
| author2 | Komissarov, Artem, 1992- Gili, Maria Ruprecht, Verena Wieser, Stefan Maurer, Sebastian |
| author2_role | author author author author author |
| author_browse | Baumann, Sebastian Gili, Maria Komissarov, Artem, 1992- Maurer, Sebastian Ruprecht, Verena Wieser, Stefan |
| author_facet | Baumann, Sebastian Komissarov, Artem, 1992- Gili, Maria Ruprecht, Verena Wieser, Stefan Maurer, Sebastian |
| author_role | author |
| collection | Recercat. Dipósit de la Recerca de Catalunya |
| description | 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. |
| eu_rights_str_mv | openAccess |
| format | article |
| id | ES_bcd3e27ecd3a7c09b0ff2df8ca04cbbb |
| institution | 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) |
| network_acronym_str | ES |
| network_name_str | España |
| oai_identifier_str | oai:recercat.cat:10230/44497 |
| publishDate | 2020 |
| publishDateSort | 2020 |
| publisher | American Association for the Advancement of Science (AAAS) |
| publisherStr | American Association for the Advancement of Science (AAAS) |
| reponame_str | Recercat. Dipósit de la Recerca de Catalunya |
| spelling | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs Baumann, Sebastian Komissarov, Artem, 1992- Gili, Maria Ruprecht, Verena Wieser, Stefan Maurer, Sebastian RNA missatger Genètica Genòmica Tumors Proteïnes 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. 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 American Association for the Advancement of Science (AAAS) http://hdl.handle.net/10230/44497 http://dx.doi.org/10.1126/sciadv.aaz1588 |
| spellingShingle | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs Baumann, Sebastian RNA missatger Genètica Genòmica Tumors Proteïnes |
| status_str | publishedVersion |
| title | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs |
| title_full | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs |
| title_fullStr | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs |
| title_full_unstemmed | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs |
| title_short | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs |
| title_sort | A reconstituted mammalian APC-kinesin complex selectively transports defined packages of axonal mRNAs |
| topic | RNA missatger Genètica Genòmica Tumors Proteïnes |
| topic_facet | RNA missatger Genètica Genòmica Tumors Proteïnes |
| url | http://hdl.handle.net/10230/44497 http://dx.doi.org/10.1126/sciadv.aaz1588 |