The septin cytoskeleton in myelinating glia

Area of Science:

• Neuroscience
• Cell Biology
• Biochemistry

Background:

• Myelin sheaths exhibit distinct subdomains with specialized protein and lipid compositions.
• The mechanisms underlying the establishment and maintenance of these myelin domains remain largely unknown.
• Cytoskeletal elements are hypothesized to play a role in generating and sustaining these structural domains through interactions with membrane components.

Purpose of the Study:

• To investigate the interaction between myelin protein MAL and the cytoskeleton.
• To explore the role of septins in myelin structure and function.
• To determine the localization and expression patterns of septins during myelin formation.

Main Methods:

• Co-immunoprecipitation assays to detect protein interactions.
• Immunofluorescence microscopy to visualize protein localization in myelin.
• Quantitative real-time PCR and Western blotting to assess protein expression levels.
• Analysis of myelin lacking specific septin proteins.

Main Results:

• The transmembrane myelin protein MAL was found to interact with the cytoskeleton protein septin 6.
• Multiple septin complexes associate with myelin, with variations between the central and peripheral nervous system.
• Septin expression is upregulated during myelin formation in peripheral nerves and oligodendrocytes.
• Septins are enriched in non-compact myelin compartments, including paranodal loops and microvilli at the node of Ranvier.
• Mice lacking Septin 6 showed increased Septin 11 abundance, indicating a compensatory mechanism.

Conclusions:

• The septin cytoskeleton is an integral component of the myelin sheath.
• Septins interact with myelin constituents like MAL, suggesting a role in myelin organization.
• Septins are proposed as key players in membrane compartmentalization within myelin internodes.