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The Journal of Neuroscience, May 28, 2008, 28(22):5731-5739; doi:10.1523/JNEUROSCI.4431-07.2008

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Cellular/Molecular
Postsynaptic Density-93 Clusters Kv1 Channels at Axon Initial Segments Independently of Caspr2

Yasuhiro Ogawa,¹ Ido Horresh,² James S. Trimmer,³ David S. Bredt,⁴ Elior Peles,² and Matthew N. Rasband¹

¹Department of Neuroscience, Baylor College of Medicine, Houston, Texas 77030, ²Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel 76100, ³Section of Neurobiology, Physiology, and Behavior, College of Biological Sciences, University of California, Davis, Davis, California 95616, and ⁴Department of Neuroscience, Eli Lilly and Company, Indianapolis, Indiana 46285

Correspondence should be addressed to Dr. Matthew N. Rasband, Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Email: Rasband{at}bcm.edu

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.

Key words: action potential; juxtaparanode; scaffold; ankyrin; cell adhesion molecule; MAGUK

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Received Sept. 27, 2007; revised Feb. 14, 2008; accepted Feb. 14, 2008.

Correspondence should be addressed to Dr. Matthew N. Rasband, Department of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030. Email: Rasband{at}bcm.edu

This article has been cited by other articles:

				C. Bel, K. Oguievetskaia, C. Pitaval, L. Goutebroze, and C. Faivre-Sarrailh Axonal targeting of Caspr2 in hippocampal neurons via selective somatodendritic endocytosis J. Cell Sci., September 15, 2009; 122(18): 3403 - 3413. [Abstract] [Full Text] [PDF]

				A. Lorincz and Z. Nusser Cell-Type-Dependent Molecular Composition of the Axon Initial Segment J. Neurosci., December 31, 2008; 28(53): 14329 - 14340. [Abstract] [Full Text] [PDF]

				I. Horresh, S. Poliak, S. Grant, D. Bredt, M. N. Rasband, and E. Peles Multiple Molecular Interactions Determine the Clustering of Caspr2 and Kv1 Channels in Myelinated Axons J. Neurosci., December 24, 2008; 28(52): 14213 - 14222. [Abstract] [Full Text] [PDF]

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