Schematic overview of the trafficking of newly synthesized PLP to myelin membranes in the presence or absence of MAL.

<p>In the absence of MAL (upper part), newly synthesized PLP is transported to the myelin membrane via an indirect pathway, involving (i) vesicular transport to the apical-like cell body plasma membrane prior to basolateral-like myelin membranes and (ii) temporal accumulation in a late endosomal compartment [<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155317#pone.0155317.ref011" target="_blank">11</a>,<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0155317#pone.0155317.ref020" target="_blank">20</a>]. Along this route, PLP partitions in distinct membrane domains, i.e., TX100-resistant or CHAPS-resistant, and expose different conformational epitopes during respectively biosynthetic (red, ET3) and transcytotic (blue, O10) transport. In the presence of MAL (lower part), the distinct partitioning of PLP in distinct membrane microdomains is lost and both conformational epitopes are exposed along the entire membrane. These MAL-mediated changes allow for lateral diffusion of PLP from the cell body plasma membrane to the myelin membrane (green, ET3/O10).