Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2

Yasuhiro Ogawa, Ido Horresh, James Trimmer, David S. Bredt, Elior Peles, Matthew N. Rasband

Research output: Contribution to journalArticle

83 Scopus citations

Abstract

Postsynaptic density-93 (PSD-93)/Chapsyn-110 is a PDZ (PSD-95/Discs large/zona occludens-1) domain-containing membrane-associated guanylate kinase (MAGUK) that functions as a scaffold to assemble channels, receptors, and other signaling proteins at cell membranes. PSD-93 is highly enriched at synapses, but mice lacking this protein have no synaptic structural abnormalities, probably because of overlapping expression and redundancy with other MAGUKs. Consequently, the function of PSD-93 is not well understood. Here, we show that PSD-93, but not other MAGUKs, is enriched at the axon initial segment (AIS), where it colocalizes with Kv1.1, Kv1.2, Kv1.4, and Kvβ2 subunit-containing K+ channels, Caspr2, and TAG-1 (transient axonal glycoprotein-1). When coexpressed with Kv1 channels in heterologous cells, PSD-93 induces formation of large cell-surface clusters. Knockdown of PSD-93 in cultured hippocampal neurons by RNA interference disrupted Kv1 channel localization at the AIS. Similarly, PSD-93-/- mice failed to cluster Kv1 channels at the AIS of cortical and hippocampal neurons. In contrast, Caspr2, which mediates Kv1 channel clustering at the juxtaparanode, is not required for localization of Kv1 channels at the AIS. These results show PSD-93 mediates AIS accumulation of Kv1 channels independently of Caspr2.

Original languageEnglish (US)
Pages (from-to)5731-5739
Number of pages9
JournalJournal of Neuroscience
Volume28
Issue number22
DOIs
StatePublished - May 28 2008

Keywords

  • Action potential
  • Ankyrin
  • Cell adhesion molecule
  • Juxtaparanode
  • MAGUK
  • Scaffold

ASJC Scopus subject areas

  • Neuroscience(all)
  • Medicine(all)

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    Ogawa, Y., Horresh, I., Trimmer, J., Bredt, D. S., Peles, E., & Rasband, M. N. (2008). Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2. Journal of Neuroscience, 28(22), 5731-5739. https://doi.org/10.1523/JNEUROSCI.4431-07.2008