6533b82efe1ef96bd1293e8b

RESEARCH PRODUCT

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

Julia PatzigKathrin KuschKlaus-armin NaveKlaus-armin NaveMichelle S ErwigHauke B. WernerPayam DibajWiebke MöbiusWiebke MöbiusStefan TenzerNicole Schaeren-wiemersSandra Goebbels

subject

0301 basic medicineNervous systemCentral Nervous SystemProteomicsScaffoldMouseProteomeNeural ConductionSeptinNerve Fibers MyelinatedMyelinGene Knockout TechniquesMiceContractile ProteinsAxonBiology (General)CytoskeletonMicroscopy ImmunoelectronCytoskeletonMyelin SheathMicroscopy ConfocalGeneral NeuroscienceQRGeneral MedicineAnatomyCell biologyglial cellsmedicine.anatomical_structureGene TargetingMedicineResearch ArticleQH301-705.5ScienceCentral nervous systemmyelinated axonsmacromolecular substancesBiologyGeneral Biochemistry Genetics and Molecular Biologymyelin structure03 medical and health sciencesSeptin/anillin filaments; central nervous system; myelinlabel-free proteomicsmedicineAnimalsneuropathologyGeneral Immunology and Microbiology030104 developmental biologynervous systemseptin cytoskeletonProtein MultimerizationSeptinsSeptin cytoskeletonNeuroscience

description

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. DOI: http://dx.doi.org/10.7554/eLife.17119.001

yearjournalcountryeditionlanguage
2016-08-01eLife
10.7554/elife.17119http://europepmc.org/articles/PMC4978525