Evolution of peripheral myelin protein 22

The evolution of the protein structure of myelination in jawed vertebrates is fascinating in part because certain vertebrates (i.e., goldfish and zebrafish) have the capability to regenerate myelin. If we could figure out the protein changes underlying this divergence, we could perhaps express genes promoting the expression of these critical proteins in humans and replicate this ability. And even if that lofty goal is not realized, the study of the evolution of myelin protein may yield insight into demyelinating diseases such as multiple sclerosis and leukodystrophy. Of course, none of this is news to those of you who have read my essay on the evolution of myelin proteins in vertebrates!

One of the proteins that I didn’t include due to space constraints and lack of detailed research was peripheral myelin protein-22 (pmp-22). In the peripheral nervous system, this protein interacts with a receptor (the integrin alpha-6 beta-4 subunit) to improve adhesion between the myelin sheath and the basil lamina.

Itou et al recently over-expressed this protein in medaka fish, with approximately 2-fold higher levels of transcription. These fish are relatively normal but have slightly diminished fitness due to diminished nerve conductance velocity and reduced ability to swim against the current. Moreover, the authors found that the sequences coding for pmp-22 have been well preserved throughout jawed vertebrates, even in non-coding motifs. This suggests that it is important to normal function and lowers the probability that differences in myelin phenotype will be due to changes in this protein.

Reference

Itou J, et al. 2009 Functional and comparative genomics analyses of pmp22 in medaka fish. BMC Neuroscience 10:60. doi:10.1186/1471-2202-10-60.