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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.

Author information

1
Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
2
Institute of Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
3
Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
4
Departement of Biomedicine, University Hospital Basel, Basel, Switzerland.

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.

KEYWORDS:

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

PMID:
27504968
PMCID:
PMC4978525
DOI:
10.7554/eLife.17119
[Indexed for MEDLINE]
Free PMC Article

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