The septin cytoskeleton in myelinating glia.
Myelin is organized in subdomains with distinct protein and lipid composition. How these domains are established and maintained is currently unknown. Cytoskeletal elements interacting with membrane components could generate and sustain such structural domains. Here, we demonstrate that the transmembrane myelin protein MAL interacts with the cytoskeleton protein septin 6. Septins represent a fourth filamentous system involved in membrane compartmentalization, vesicle transport and scaffold formation. We report that multiple septin complexes are associated with myelin, and that they display an overlapping but non-identical composition in the central and peripheral nervous system. The expression of distinct subsets of septins was upregulated during myelin formation in peripheral nerves and oligodendrocytes. In the PNS, septins were highly enriched in non-compact myelin compartments, particularly in the paranodal loops and the microvilli at the node of Ranvier. Importantly in myelin lacking Septin 6, the abundance of its closest homolog Sept11 was increased, suggesting a functional compensatory role. Our data demonstrate that the septin cytoskeleton is an integral component of the myelin sheath and interacts with distinct myelin constituents such as MAL. We suggest that septins are intriguing candidates for membrane compartmentalization in myelin internodes.
Buser
A M
AM
Neurobiology, Department of Biomedicine and Neurology, University Hospital Basel, Pharmacenter 7007, Klingelbergstrasse 50/70, CH-4056 Basel, Switzerland.
Erne
B
B
Werner
H B
HB
Nave
K-A
KA
Schaeren-Wiemers
N
N
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000235:genetics / Q000378:metabolism; D003599:Cytoskeleton / Q000378:metabolism*; D020558:GTP Phosphohydrolases / Q000235:genetics / Q000378:metabolism; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D026901:Membrane Transport Proteins / Q000235:genetics / Q000378:metabolism; D051379:Mice; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism; D009186:Myelin Sheath / Q000378:metabolism*; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D009457:Neuroglia / Q000166:cytology / Q000502:physiology*; D017933:Peripheral Nervous System / Q000378:metabolism; D011485:Protein Binding; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D011510:Proteolipids / Q000235:genetics / Q000378:metabolism; D051381:Rats; D058112:Septins; D020798:Two-Hybrid System Techniques
D015415:Biomarkers; D003598:Cytoskeletal Proteins; C569026:MAL protein, human; C569027:Mal protein, mouse; C569028:Mal protein, rat; D026901:Membrane Transport Proteins; D009185:Myelin Proteins; D062806:Myelin and Lymphocyte-Associated Proteolipid Proteins; D020033:Protein Isoforms; D011510:Proteolipids; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; C106863:Sept2 protein, mouse; C486672:Sept6 protein, mouse; D058112:Septins