title: Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction.
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.
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
authors: Julia
authors: J
authors: Patzig
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
authors: Michelle S
authors: MS
authors: Erwig
authors: Institute of Immunology, University Medical Center, Johannes Gutenberg University, Mainz, Germany.
authors: Stefan
authors: S
authors: Tenzer
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
authors: Kathrin
authors: K
authors: Kusch
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
authors: Payam
authors: P
authors: Dibaj
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
authors: Wiebke
authors: W
authors: Möbius
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
authors: Sandra
authors: S
authors: Goebbels
authors: Departement of Biomedicine, University Hospital Basel, Basel, Switzerland.
authors: Nicole
authors: N
authors: Schaeren-Wiemers
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.|Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Göttingen, Germany.
authors: Klaus-Armin
authors: KA
authors: Nave
authors: Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Goettingen, Germany.
authors: Hauke B
authors: 0000-0002-7710-5738
authors: HB
authors: Werner
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000737:chemistry / Q000502:physiology*; D003285:Contractile Proteins / Q000378:metabolism*; D003599:Cytoskeleton / Q000378:metabolism; D055786:Gene Knockout Techniques; D018390:Gene Targeting; D051379:Mice; D018613:Microscopy, Confocal; D016253:Microscopy, Immunoelectron; D009186:Myelin Sheath / Q000378:metabolism*; D009413:Nerve Fibers, Myelinated / Q000737:chemistry / Q000502:physiology; D009431:Neural Conduction; D055503:Protein Multimerization; D020543:Proteome / Q000032:analysis; D040901:Proteomics; D058112:Septins / Q000235:genetics / Q000378:metabolism*
chemical_list: D003285:Contractile Proteins; D020543:Proteome; C095886:anillin; D058112:Septins
keywords: glial cells; label-free proteomics; mouse; myelin structure; myelinated axons; neuropathology; neuroscience; septin cytoskeleton