A novel protein interaction in myelin
One long-standing question in myelin biochemistry was solved, as a new binding partner specific for the large isoform of MAG was identified.
Myelination requires a coordinated interplay of specific proteins and lipid membranes. The myelin-associated glycoprotein (MAG) is a large integral membrane protein in the myelin sheath, which attaches to the axonal surface. MAG has two alternatively spliced isoforms, and thus far, the role of the two isoforms has been enigmatic at the molecular level.
In collaboration with the Max Planck Instititute for Experimental Medicine in Göttingen, Germany, we identified a high-affinity binding partner for the L-MAG isoform. DYNLL1 forms a heterotetrameric complex with the L-MAG cytoplasmic domain, and this isoform-specific dimerization could have crucial effects on extracellular domain adhesion to the axonal surface during development and myelin maintenance. The protein-protein complex was characterized in detail using biophysical techniques, as well as high-resolution synchrotron X-ray crystallography and small-angle X-ray scattering.
Our study has provided an important new insight into molecular interactions in myelin. At the personal level, this is even more important, since Petri has, indeed, approached this specific problem - understanding the MAG isoforms at the molecular level - already since he did his PhD in Finland in the 1990s. It is important to have long-term, curiosity-driven goals in science, and it is equally important to have suitable conditions available to work towards those goals.
The original article:
The editorial by the Journal of Neurochemistry to highlight the importance of the study: