The P0 Gene

Protein zero (P0) is the major structural protein in myelin of the peripheral nervous system (PNS). P0 has three domains: extracellular, transmembrane, and cytoplasmic. To date, only the recombinant extracellular domain corresponding to the sequence for rat has been crystallized. This chapter focuses on what is now known about P0, and updating what has been presented in some earlier and recent reviews. To understand the structural role of P0 in myelin membrane adhesion and its mechanism of action, a model system should be developed in which alterations in P0 can be engineered and introduced transgenically into an animal, and in which ramifications across the hierarchy of myelin development, nerve function, and myelin membrane structure and interactions can be determined. While use of in vitro systems has provided some clues and considerable progress has been made using transgenic mice, it can be anticipated that exploitation of the zebrafish vertebrate model for myelination may also lead to additional rapid progress.