Septin/anillin filaments scaffold central nervous system myelin to accelerate nerve conduction
- Max Planck Institute of Experimental Medicine, Germany
- University Medical Center, Johannes Gutenberg University, Germany
- Center for Nanoscale Microscopy and Molecular Physiology of the Brain, Germany
- University Hospital Basel, Switzerland
Figures
Figure 1 with 1 supplement
Mouse mutants with complex CNS pathology exhibit distinct but overlapping changes of myelin composition.
(A) Venn diagram summarizing CNS pathology in mice lacking the myelin proteins CNP, MAG, or PLP, according to quantitative evaluation of electron micrographs of optic nerves at P75. Note that myelin …
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Figure 1—source data 1
Dataset file (differential myelin proteome analyses) related to Figure 1C, Figure 1—figure supplement 1F, and Figure 6E.
- https://doi.org/10.7554/eLife.17119.004
Figure 1—figure supplement 1
Neuropathological and molecular analysis in mouse models of complex CNS pathology (Cnpnull, Magnull, and Plp1null mice).
(A–E) Quantification of CNS pathology as summarized in main Figure 1A. Electron micrographs of optic nerves were evaluated for the indicated pathologies. Note that myelin outfoldings are common to …
Figure 2 with 1 supplement
Septins form longitudinal filaments in the adaxonal compartment of mature CNS myelin.
(A–C) Immunofluorescent signal of SEPT8 and SEPT7 (green) extends longitudinally alongside axons identified by neurofilament-labelling (red). All panels show maximal projections of confocal stacks, …
Figure 2—figure supplement 1
Localization of myelin septins.
(A,B) Localization of SEPT7 and SEPT8 by cryo-immuno electron microscopy. (a) Immunodetection of SEPT8 (15 nm gold particles, white arrowheads) together with SEPT7 (10 nm gold particles, black …
Figure 3
Septins in myelin development and aging.
(A) Scheme showing the localization of septin filaments (red) in healthy adaxonal myelin. Note that all experimental data support a model that myelin septins (SEPT2, SEPT4, SEPT7, SEPT8) assemble as …
Figure 4
Anillin co-distributes with myelin septins.
(A) Confocal microscopy reveals proximity-labelling of SEPT8 (green) and anillin (red). The merge additionally shows the axonal marker Tuj1 (white). Longitudinally sectioned optic nerves of P75 WT …
Figure 5
Membrane phosphoinositides mediate septin/anillin assembly in myelin.
(A) Scheme of the reaction catalyzed by the phosphatase PTEN, which converts PI(3,4,5)P3 into PI(4,5)P2. The reverse reaction is mediated by phosphatidylinositol-3-kinase (PI3K). Previous reports …
Figure 6 with 1 supplement
Myelination in mice lacking myelin-associated septins.
(A) Silver impregnation visualizes myelinated fibre tracts in mice lacking SEPT8 from myelinating cells (Sept8flox/flox;CnpCre/WT-mice; COND) or from all cells (Sept8null/null-mice; KO). Images are …
Figure 6—figure supplement 1
Generation of mice lacking expression of SEPT8.
(A) Scheme of the engineered Sept8-allele before and after recombination (see Materials and methods section for details). (B) Genotyping PCR identifying the indicated alleles. (C) Histochemistry to …
Figure 7 with 2 supplements
Lack of myelin septins causes myelin outfoldings and decelerated nerve conduction.
(A) Electron micrographs of optic nerves exemplify myelin outfoldings at P75. Stippled lines highlight myelin outfoldings; associated axons are marked with asterisks. (B) Quantitative evaluation of …
Figure 7—figure supplement 1
SEPT8 deficiency does not induce astrogliosis, microgliosis or altered structure or density of the nodes of Ranvier.
(A–B) Immunohistochemical analysis of GFAP-immunopositivity (B) and MAC3-immunopositivity (B) in the white matter (hippocampal fimbria) of wild-type (WT), Sept8null/null(KO), and Sept8flox/flox;CnpCr…
Figure 7—figure supplement 2
Dynamics of septin filament degradation in myelin and emergence of myelin outfoldings in adult mice.
(A) Experimental scheme of Tamoxifen injection into adult Sept8flox/flox;PlpCre-ERT2 and Sept8flox/flox control mice, immunoblotting, and transmission electron microscopic analysis (TEM). wks pti, …
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