Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons
AuthorsHahn, Ines; orcid: 0000-0001-7703-8160; email: Ines.Hahn@manchester.ac.uk
Voelzmann, Andre; orcid: 0000-0002-7682-5637
Fülle, Judith B.; orcid: 0000-0003-1609-1368
Slater, Paula G.; orcid: 0000-0003-2601-0613
Lowery, Laura Anne; orcid: 0000-0001-8959-2679
Sanchez-Soriano, Natalia; orcid: 0000-0002-6667-2817; email: N.Sanchez-Soriano@liverpool.ac.uk
Prokop, Andreas; email: Andreas.Prokop@manchester.ac.uk
MetadataShow full item record
AbstractThe formation and maintenance of microtubules requires their polymerisation, but little is known about how this polymerisation is regulated in cells. Focussing on the essential microtubule bundles in axons of Drosophila and Xenopus neurons, we show that the plus-end scaffold Eb1, the polymerase XMAP215/Msps and the lattice-binder Tau co-operate interdependently to promote microtubule polymerisation and bundle organisation during axon development and maintenance. Eb1 and XMAP215/Msps promote each other’s localisation at polymerising microtubule plus-ends. Tau outcompetes Eb1-binding along microtubule lattices, thus preventing depletion of Eb1 tip pools. The three factors genetically interact and show shared mutant phenotypes: reductions in axon growth, comet sizes, comet numbers and comet velocities, as well as prominent deterioration of parallel microtubule bundles into disorganised curled conformations. This microtubule curling is caused by Eb1 plus-end depletion which impairs spectraplakin-mediated guidance of extending microtubules into parallel bundles. Our demonstration that Eb1, XMAP215/Msps and Tau co-operate during the regulation of microtubule polymerisation and bundle organisation, offers new conceptual explanations for developmental and degenerative axon pathologies.
CitationPLOS Genetics, volume 17, issue 7, page e1009647
PublisherPublic Library of Science
DescriptionFrom PLOS via Jisc Publications Router
History: received 2021-04-23, accepted 2021-06-07, collection 2021-07, epub 2021-07-06
Publication status: Published
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/I002448/1
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/P020151/1
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/L000717/1
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/M007553/1
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/M007456/1
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268; Grant(s): BB/R018960/1
Funder: Leverhulme Trust; funder-id: http://dx.doi.org/10.13039/501100000275; Grant(s): ECF-2017-247
Funder: Deutsche Forschungsgemeinschaft; funder-id: http://dx.doi.org/10.13039/501100001659; Grant(s): VO 2071/1-1
Funder: National Institutes of Health; funder-id: http://dx.doi.org/10.13039/100000002; Grant(s): R01 MH109651
Funder: Consejo Nacional de Innovación, Ciencia y Tecnología; funder-id: http://dx.doi.org/10.13039/501100009068
Funder: Biotechnology and Biological Sciences Research Council; funder-id: http://dx.doi.org/10.13039/501100000268
Funder: Wellcome Trust; funder-id: http://dx.doi.org/10.13039/100010269
Funder: University of Manchester Strategic Fund
Funder: Wellcome Trust; funder-id: http://dx.doi.org/10.13039/100004440; Grant(s): 087742/Z/08/Z
Funder: National Institutes of Health; funder-id: http://dx.doi.org/10.13039/100000002; Grant(s): P40OD018537
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