Molecular Architecture of Myelinated Nerve Fibers Leaky Paranodal Junctions and Paranodal Dysmyelination

• Published in: The Neuroscientist (Baltimore, Md.) Vol. 19; no. 6; pp. 629 - 641
• Main Authors: Rosenbluth, Jack, Mierzwa, Amanda, Shroff, Seema
• Format: Journal Article
• Language: English
• Published: Los Angeles, CA SAGE Publications 01-12-2013
• Subjects: Animals; Axons - ultrastructure; Humans; Mice; Nerve Fibers, Myelinated - pathology; Nerve Fibers, Myelinated - physiology; Nerve Fibers, Myelinated - ultrastructure; Neuroglia - ultrastructure; Ranvier's Nodes - ultrastructure; myelin; nerve fibers; demyelination; multiple sclerosis
• ISSN: 1073-8584; 1089-4098
• DOI: 10.1177/1073858413504627

Myelinated nerve fibers have evolved to optimize signal propagation. Each myelin segment is attached to the axon by the unique paranodal axoglial junction (PNJ), a highly complex structure that serves to define axonal ion channel domains and to direct nodal action currents through adjacent nodes. Surprisingly, this junction does not entirely seal the paranodal myelin sheath to the axon and thus does not entirely isolate the perinodal space from the internodal periaxonal space. Rather the paranode is penetrated by extracellular pathways between the myelin sheath and the axolemma for movement of molecules and the flow of current to and from the internodal axon. This review summarizes past and current studies demonstrating these pathways and considers what functional roles they subserve. In addition, modern genetic engineering methods permit modification of individual PNJ constituents, which provides an opportunity to define their specific functions. One component in particular, the transverse bands, plays a key role in maintaining the structure and function of the PNJ. Loss of transverse bands results not in frank demyelination but rather in subtle dysmyelination, which causes significant functional impairment. The consequences of such subtle defects in the PNJ are considered along with the relevance of these studies to human diseases of myelin.