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Elife. 2016 Aug 9;5. pii: e17119. doi: 10.7554/eLife.17119.

Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction.

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Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
Institute of Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
Departement of Biomedicine, University Hospital Basel, Basel, Switzerland.


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.


glial cells; label-free proteomics; mouse; myelin structure; myelinated axons; neuropathology; neuroscience; septin cytoskeleton

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