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

2016 | journal article. A publication with affiliation to the University of Göttingen.

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​Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction​
Patzig, J.; Erwig, M. S; Tenzer, S.; Kusch, K.; Dibaj, P.; Möbius, W.   & Goebbels, S. et al.​ (2016) 
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Patzig, Julia; Erwig, Michelle S; Tenzer, Stefan; Kusch, Kathrin; Dibaj, Payam; Möbius, Wiebke ; Goebbels, Sandra; Schaeren-Wiemers, Nicole; Nave, Klaus-Armin; Werner, Hauke B
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.
Normal communication within the brain or between the brain and other parts of the body requires information to flow quickly around the nervous system. This information travels along nerve cells in the form of electrical signals. To speed up the signals, a part of the nerve cell called the axon is frequently wrapped in an electrically insulating sheath made up of a membrane structure called myelin. The myelin sheath becomes impaired as a result of disease or ageing. In order to understand what might produce these changes, Patzig et al. have used biochemical and microscopy techniques to study mice that had similar defects in their myelin sheaths. The study reveals that forming a normal myelin sheath around an axon requires a newly identified ‘scaffold’ made of a group of proteins called the septins. Combining with another protein called anillin, septins assemble into filaments in the myelin sheath. These filaments then knit together into a scaffold that grows lengthways along the myelin-wrapped axon. Without this scaffold, the myelin sheath grew defects known as outfoldings. Axons transmitted electrical signals much more slowly than normal when the septin scaffold was missing from the myelin sheath. Future studies are needed to understand the factors that control how the septin scaffold forms. This could help to reveal ways of reversing the changes that alter the myelin sheath during ageing and disease.
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