Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons
| Autor: | Judith B Fuelle, André Voelzmann, Laura Anne Lowery, Ines Hahn, Andreas Prokop, Natalia Sanchez-Soriano, Paula G. Slater, Jill Parkin |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Cancer Research Life Cycles Drosophila Proteins/metabolism Xenopus Mutant Neurons/metabolism Xenopus Proteins QH426-470 Microtubules Polymerization Xenopus laevis 0302 clinical medicine Nerve Fibers Larvae Animal Cells Drosophila Proteins Axon Genetics (clinical) Cytoskeleton Neurons 0303 health sciences Chemistry Drosophila Melanogaster Neurodegeneration Chemical Reactions Eukaryota Animal Models Axon growth Cell biology Insects Phenotypes medicine.anatomical_structure Experimental Organism Systems Microtubules/metabolism Physical Sciences Vertebrates Microtubule-Associated Proteins/metabolism Frogs Drosophila Drosophila melanogaster Cellular Types Cellular Structures and Organelles Xenopus laevis/metabolism Microtubule-Associated Proteins Research Article Arthropoda tau Proteins Axons/metabolism macromolecular substances Biology Xenopus Proteins/metabolism Research and Analysis Methods Drosophila melanogaster/metabolism Amphibians 03 medical and health sciences Model Organisms tau Proteins/metabolism Microtubule medicine Genetics Animals Molecular Biology Ecology Evolution Behavior and Systematics 030304 developmental biology fungi Organisms Biology and Life Sciences Cell Biology medicine.disease biology.organism_classification Polymer Chemistry Invertebrates Axons 030104 developmental biology Bundle Cellular Neuroscience Axoplasmic transport Animal Studies Zoology Entomology 030217 neurology & neurosurgery Neuroscience Developmental Biology |
| Zdroj: | PLoS Genetics, Vol 17, Iss 7, p e1009647 (2021) Hahn, I, Voelzmann, A, Parkin, J, Fülle, J B, Slater, P G, Lowery, L A, Sanchez-Soriano, N & Prokop, A 2021, ' Tau, XMAP215/Msps and Eb1 co-operate interdependently to regulate microtubule polymerisation and bundle formation in axons ', PLoS Genetics, vol. 17, no. 7, 1009647 . https://doi.org/10.1371/journal.pgen.1009647 PLoS Genetics PLOS GENETICS |
| ISSN: | 1553-7404 1553-7390 |
| DOI: | 10.1371/journal.pgen.1009647 |
| Popis: | The 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. Author summary Axons are the up-to-meter-long processes of nerve cells that form the cables wiring our nervous system. Once established, they must survive for a century in humans. Improper extension of axons leads to neurodevelopmental defects, and age- or disease-related neurodegeneration usually starts in axons. Axonal architecture and function depend on bundles of filamentous polymers, called microtubules. These bundles run all along the axonal core, and their disruption correlates with axon decay. How these axonal microtubule bundles are formed and dynamically maintained is little understood. We bridge this knowledge gap by studying how different classes of microtubule-binding proteins may regulate these processes. Here we show how three proteins of very different function, Eb1, XMAP215 and Tau, cooperate intricately to promote the polymerisation processes that form new microtubules during axon development and maintenance. If either protein is dysfunctional, polymerisation is slowed down and newly forming microtubules fail to align into proper bundles. These findings provide new explanations for the decay of microtubule bundles, hence axons. To unravel these mechanisms, we used the fruit fly as a powerful organism for biomedical discoveries. We then showed that the same mechanisms act in frog axons, suggesting they might apply also to humans. |
| Databáze: | OpenAIRE |
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