A Glial Signal Consisting of Gliomedin and NrCAM Clusters Axonal Na+ Channels during the Formation of Nodes of Ranvier

被引:164
作者
Feinberg, Konstantin [1 ]
Eshed-Eisenbach, Yael [1 ]
Frechter, Shahar [1 ]
Amor, Veronique [1 ]
Salomon, Daniela [1 ]
Sabanay, Helena [1 ]
Dupree, Jeffrey L. [2 ]
Grumet, Martin [3 ]
Brophy, Peter J. [4 ]
Shrager, Peter [5 ]
Peles, Elior [1 ]
机构
[1] Weizmann Inst Sci, Dept Mol Cell Biol, IL-76100 Rehovot, Israel
[2] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA
[3] Rutgers State Univ, WM Keck Ctr Collaborat Neurosci, Piscataway, NJ 08854 USA
[4] Univ Edinburgh, Neurosci Res Ctr, Edinburgh EH9 1QH, Midlothian, Scotland
[5] Univ Rochester, Med Ctr, Dept Neurobiol & Anat, Rochester, NY 14642 USA
关键词
CELL-ADHESION MOLECULES; PERIPHERAL NERVOUS-SYSTEM; BETA-IV-SPECTRIN; MYELINATED AXONS; INITIAL SEGMENTS; SODIUM-CHANNELS; ANKYRIN-G; K+ CHANNELS; NR-CAM; NEUROFASCIN;
D O I
10.1016/j.neuron.2010.02.004
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Saltatory conduction requires high-density accumulation of Na+ channels at the nodes of Ranvier. Nodal Na+ channel clustering in the peripheral nervous system is regulated by myelinating Schwann cells through unknown mechanisms. During development, Na+ channels are first clustered at heminodes that border each myelin segment, and later in the mature nodes that are formed by the fusion of two heminodes. Here, we show that initial clustering of Na+ channels at heminodes requires glial NrCAM and gliomedin, as well as their axonal receptor neurofascin 186 (NF186). We further demonstrate that heminodal clustering coincides with a second, paranodal junction (PNJ)-dependent mechanism that allows Na+ channels to accumulate at mature nodes by restricting their distribution between two growing myelin internodes. We propose that Schwann cells assemble the nodes of Ranvier by capturing Na+ channels at heminodes and by constraining their distribution to the nodal gap. Together, these two cooperating mechanisms ensure fast and efficient conduction in myelinated nerves.
引用
收藏
页码:490 / 502
页数:13
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