PT  - JOURNAL ARTICLE
AU  - Yasuhiro Ogawa
AU  - Ido Horresh
AU  - James S. Trimmer
AU  - David S. Bredt
AU  - Elior Peles
AU  - Matthew N. Rasband
TI  - Postsynaptic Density-93 Clusters Kv1 Channels at Axon Initial Segments Independently of Caspr2
AID  - 10.1523/JNEUROSCI.4431-07.2008
DP  - 2008 May 28
TA  - The Journal of Neuroscience
PG  - 5731--5739
VI  - 28
IP  - 22
4099  - http://www.jneurosci.org/content/28/22/5731.short
4100  - http://www.jneurosci.org/content/28/22/5731.full
SO  - J. Neurosci.2008 May 28; 28
AB  - 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.