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

First Author  Ogawa Y Year  2008
Journal  J Neurosci Volume  28
Issue  22 Pages  5731-9
PubMed ID  18509034 Mgi Jnum  J:149503
Mgi Id  MGI:3848609 Doi  10.1523/JNEUROSCI.4431-07.2008
Citation  Ogawa Y, et al. (2008) Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2. J Neurosci 28(22):5731-9
abstractText  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 Kvbeta2 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.
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