期刊
JOURNAL OF NEUROSCIENCE
卷 28, 期 22, 页码 5731-5739出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.4431-07.2008
关键词
action potential; juxtaparanode; scaffold; ankyrin; cell adhesion molecule; MAGUK
资金
- NINDS NIH HHS [R01 NS034383, R37 NS034383, R01 NS034383-13A2, NS044916, R01 NS044916-08, NS034383, R01 NS044916, R37 NS044916] Funding Source: Medline
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 Kv beta 2 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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