Recent progress on the molecular organization of myelinated axons

作者：Steven S. Scherer, Edgardo J. Arroyo · 发表于：Journal of the Peripheral Nervous System · 年份：2002 · DOI：10.1046/j.1529-8027.2002.02001.x · 被引用次数：193 · 研究领域：Hereditary Neurological Disorders、Signaling Pathways in Disease、Axon Guidance and Neuronal Signaling

The structure of myelinated axons was well described 100 years ago by Ramón y Cajal, and now their molecular organization is being revealed. The basal lamina of myelinating Schwann cells contains laminin-2, and their abaxonal/outer membrane contains two laminin-2 receptors, alpha6beta4 integrin and dystroglycan. Dystroglycan binds utrophin, a short dystrophin isoform (Dp116), and dystroglycan-related protein 2 (DRP2), all of which are part of a macromolecular complex. Utrophin is linked to the actin cytoskeleton, and DRP2 binds to periaxin, a PDZ domain protein associated with the cell membrane. Non-compact myelin--found at incisures and paranodes--contains adherens junctions, tight junctions, and gap junctions. Nodal microvilli contain F-actin, ERM proteins, and cell adhesion molecules that may govern the clustering of voltage-gated Na+ channels in the nodal axolemma. Na(v)1.6 is the predominant voltage-gated Na+ channel in mature nerves, and is linked to the spectrin cytoskeleton by ankyrinG. The paranodal glial loops contain neurofascin 155, which likely interacts with heterodimers composed of contactin and Caspr/paranodin to form septate-like junctions. The juxtaparanodal axonal membrane contains the potassium channels Kv1.1 and Kv1.2, their associated beta2 subunit, as well as Caspr2. Kv1.1, Kv1.2, and Caspr2 all have PDZ binding sites and likely interact with the same PDZ binding protein. Like Caspr, Caspr2 has a band 4.1 binding domain, and both Caspr and Caspr2 probab...