Patzig, Julia and Erwig, Michelle S. and Tenzer, Stefan and Kusch, Kathrin and Dibaj, Payam and Möbius, Wiebke and Goebbels, Sandra and Schaeren-Wiemers, Nicole and Nave, Klaus-Armin and Werner, Hauke B.. (2016) Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction. eLife, 5. e17119.
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Official URL: https://edoc.unibas.ch/62086/
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Abstract
Myelination of axons facilitates rapid impulse propagation in the nervous system. The axon/myelin-unit becomes impaired in myelin-related disorders and upon normal aging. However, the molecular cause of many pathological features, including the frequently observed myelin outfoldings, remained unknown. Using label-free quantitative proteomics, we find that the presence of myelin outfoldings correlates with a loss of cytoskeletal septins in myelin. Regulated by phosphatidylinositol-(4,5)-bisphosphate (PI(4,5)P2)-levels, myelin septins (SEPT2/SEPT4/SEPT7/SEPT8) and the PI(4,5)P2-adaptor anillin form previously unrecognized filaments that extend longitudinally along myelinated axons. By confocal microscopy and immunogold-electron microscopy, these filaments are localized to the non-compacted adaxonal myelin compartment. Genetic disruption of these filaments in Sept8-mutant mice causes myelin outfoldings as a very specific neuropathology. Septin filaments thus serve an important function in scaffolding the axon/myelin-unit, evidently a late stage of myelin maturation. We propose that pathological or aging-associated diminishment of the septin/anillin-scaffold causes myelin outfoldings that impair the normal nerve conduction velocity.
Faculties and Departments: | 03 Faculty of Medicine > Departement Biomedizin > Department of Biomedicine, University Hospital Basel > Neurobiology (Schaeren-Wiemers) |
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UniBasel Contributors: | Schaeren-Wiemers, Nicole |
Item Type: | Article, refereed |
Article Subtype: | Research Article |
ISSN: | 2050-084X |
Note: | Publication type according to Uni Basel Research Database: Journal article |
Identification Number: |
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Last Modified: | 31 May 2020 17:37 |
Deposited On: | 31 May 2020 17:37 |
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