The cytoplasmic tail of myelin protein zero induces morphological changes in lipid membranes

Area of Science:

• Neuroscience
• Biochemistry
• Structural Biology

Background:

• Protein zero (P0) is the main myelin protein in the peripheral nervous system, crucial for compact myelin stability.
• Alterations in P0, particularly its C-terminal tail (P0ct), are linked to neurodegenerative diseases like Charcot-Marie-Tooth disease.
• P0's function as an adhesion molecule and its role in myelin stability are critical for nerve health.

Purpose of the Study:

• To investigate the effects of P0ct on lipid membrane properties and structure.
• To explore the potential relevance of P0ct-induced structures in myelination.
• To characterize the structure of full-length human P0 for further research.

Main Methods:

• Studied the effects of high P0ct concentrations on bicelle membrane properties.
• Utilized time-lapse fluorescence microscopy to observe membrane dynamics.
• Performed recombinant production and low-resolution structural characterization of full-length human P0.

Main Results:

• High P0ct concentrations altered bicelle membrane properties, inducing a lamellar-to-inverted hexagonal phase transition.
• Observed fusion of bicelles into long, filament-like structures containing P0ct.
• Identified potential semicrystalline lipid domains and effects on membrane properties during myelination.

Conclusions:

• P0ct plays a significant role in stacking lipid membranes and influencing membrane properties during myelination.
• The observed filament-like structures may be relevant to the formation of semicrystalline lipid domains in myelin.
• Recombinant full-length P0 provides new tools for in vitro studies of myelin formation and maintenance.