Periodic actin structures in neuronal axons are required to maintain microtubules
| Autor: | Stephen E. D. Webb, Ines Hahn, Simon P. Pearce, Yue Qu, Andreas Prokop |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Nervous system ResearchInstitutes_Networks_Beacons/02/05 Arp2/3 complex Microtubules Microtubule polymerization Actin remodeling of neurons 0302 clinical medicine Tubulin Drosophila Proteins Spectrin Axon Cytoskeleton Cells Cultured Neurons 0303 health sciences Microfilament Proteins cytoskeleton Articles Cell biology Actin Cytoskeleton medicine.anatomical_structure Drosophila actin Microtubule-Associated Proteins axons Dementia@Manchester macromolecular substances Biology Biochemistry Genetics and Molecular Biology (miscellaneous) microtubules 03 medical and health sciences Microtubule Genetics medicine Animals development Molecular Biology Actin 030304 developmental biology Regeneration (biology) Cell Biology Actins Axons Ageing 030104 developmental biology nervous system biology.protein 030217 neurology & neurosurgery |
| Zdroj: | Molecular Biology of the Cell Qu, Y, Hahn, I, Webb, S, Pearce, S & Prokop, A 2017, ' Periodic actin structures in neuronal axons are required to maintain microtubules ', Molecular Biology of the Cell, vol. 28, no. 296-308, mbc.E16-10-0727, pp. 296-308 . https://doi.org/10.1091/mbc.E16-10-0727 |
| ISSN: | 1939-4586 1059-1524 |
| Popis: | Drosophila genetics is combined with high-resolution microscopy and a number of functional readouts to demonstrate key factors required for the presence of regularly spaced rings of cortical actin in axons. The data suggest important roles for the actin rings in microtubule regulation, most likely by sustaining their polymerization. Axons are cable-like neuronal processes wiring the nervous system. They contain parallel bundles of microtubules as structural backbones, surrounded by regularly spaced actin rings termed the periodic membrane skeleton (PMS). Despite being an evolutionarily conserved, ubiquitous, highly ordered feature of axons, the function of PMS is unknown. Here we studied PMS abundance, organization, and function, combining versatile Drosophila genetics with superresolution microscopy and various functional readouts. Analyses with 11 actin regulators and three actin-targeting drugs suggest that PMS contains short actin filaments that are depolymerization resistant and sensitive to spectrin, adducin, and nucleator deficiency, consistent with microscopy-derived models proposing PMS as specialized cortical actin. Upon actin removal, we observed gaps in microtubule bundles, reduced microtubule polymerization, and reduced axon numbers, suggesting a role of PMS in microtubule organization. These effects become strongly enhanced when carried out in neurons lacking the microtubule-stabilizing protein Short stop (Shot). Combining the aforementioned actin manipulations with Shot deficiency revealed a close correlation between PMS abundance and microtubule regulation, consistent with a model in which PMS-dependent microtubule polymerization contributes to their maintenance in axons. We discuss potential implications of this novel PMS function along axon shafts for axon maintenance and regeneration. |
| Databáze: | OpenAIRE |
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