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The Journal of Neuroscience, November 5, 2003, 23(31):10032-10039

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Cellular/Molecular
The Role of the Ankyrin-Binding Protein NrCAM in Node of Ranvier Formation

Andrew W. Custer,1 Katia Kazarinova-Noyes,2 Takeshi Sakurai,3 Xiaorong Xu,1 William Simon,2 Martin Grumet,4 and Peter Shrager1

Departments of 1Neurobiology and Anatomy and 2Biochemistry and Biophysics, University of Rochester Medical Center, Rochester, New York 14642, 3Department of Neurobiology, Mount Sinai School of Medicine, New York, New York 10029, and 4W. M. Keck Center for Collaborative Neuroscience, Rutgers University, Piscataway, New Jersey 08854

Molecular events involved in Na+ channel clustering at the node of Ranvier have been investigated during early development. NrCAM, an ankyrinG-binding protein, precedes Na+ channels at cluster sites adjacent to the tips of Schwann cell processes. Both Na+ channel and ankyrinG sequestration at developing nodes are delayed in NrCAM null mutants. The action of NrCAM is manifest locally at individual nodes, rather than affecting overall neuronal expression, and is linked to glial interactions. During remyelination, Na+ channel clusters at new nodes are initially labile, and anchoring to the cytoskeleton appears to grow progressively with time. The distance between Na+ channel clusters across remyelinating Schwann cells (nascent internodes) increases markedly from 83 to 274 µm during node formation, arguing against schemes in which the loci of nodes are fixed in advance by the axon. A hypothesis for node formation in which axonal Na+ channels move by lateral diffusion from regions of Schwann cell contact, with clustering dependent on linkage to the cytoskeleton by ankyrinG, is proposed and tested in a computational model. To match experimental measurements, this latter reaction needs fast kinetics, and the early arrival of NrCAM is postulated to contribute to this requirement.

Key words: NrCAM; node; Na channel; ankyrin; cluster; glia


Received June 19, 2003; revised September 9, 2003; accepted September 11, 2003.




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