Organizing principles of the axoglial apparatus

On axonal surfaces that flank the node of Ranvier and in overlying glial pa ranodal loops, proteins are arranged within circumscribed microdomains that defy explanation by conventional biosynthetic mechanisms. We postulate tha t the constraint of proteins to these loci is accomplished in part by discr iminative membrane-embedded molecular sieves and diffusion barriers, which serve to organize and redistribute proteins after delivery by vesicular tra nsport to neural cell plasma membranes. One sieve likely comprises a moveab le, macromolecular scaffold of axonal and glial cell-derived transmembrane adhesion molecules and their associated cytoplasmic binding partners, locat ed at the ends of each elongating myelin internode; this sieve contributes to restricting the sodium channel complexes to the node. We also anticipate the existence of a passive paranodal diffusion barrier at the myelin/nonco mpact membrane border, which prohibits protein diffusion out of contiguous paranodal membranes.