Clustering of neuronal potassium channels is independent of their interaction with PSD-95.

Matthew N. Rasband, Eunice W. Park, Dongkai Zhen, Margaret I. Arbuckle, Sebastian Poliak, Elior Peles, Seth G N Grant, James Trimmer

Research output: Contribution to journalArticle

68 Scopus citations

Abstract

Voltage-dependent potassium channels regulate membrane excitability and cell-cell communication in the mammalian nervous system, and are found highly localized at distinct neuronal subcellular sites. Kv1 (mammalian Shaker family) potassium channels and the neurexin Caspr2, both of which contain COOH-terminal PDZ domain binding peptide motifs, are found colocalized at high density at juxtaparanodes flanking nodes of Ranvier of myelinated axons. The PDZ domain-containing protein PSD-95, which clusters Kv1 potassium channels in heterologous cells, has been proposed to play a major role in potassium channel clustering in mammalian neurons. Here, we show that PSD-95 colocalizes precisely with Kv1 potassium channels and Caspr2 at juxtaparanodes, and that a macromolecular complex of Kv1 channels and PSD-95 can be immunopurified from mammalian brain and spinal cord. Surprisingly, we find that the high density clustering of Kv1 channels and Caspr2 at juxtaparanodes is normal in a mutant mouse lacking juxtaparanodal PSD-95, and that the indirect interaction between Kv1 channels and Caspr2 is maintained in these mutant mice. These data suggest that the primary function of PSD-95 at juxtaparanodes lies outside of its accepted role in mediating the high density clustering of Kv1 potassium channels at these sites.

Original languageEnglish (US)
Pages (from-to)663-672
Number of pages10
JournalJournal of Cell Biology
Volume159
Issue number4
StatePublished - Nov 25 2002
Externally publishedYes

ASJC Scopus subject areas

  • Cell Biology

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    Rasband, M. N., Park, E. W., Zhen, D., Arbuckle, M. I., Poliak, S., Peles, E., Grant, S. G. N., & Trimmer, J. (2002). Clustering of neuronal potassium channels is independent of their interaction with PSD-95. Journal of Cell Biology, 159(4), 663-672.