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 language | English (US) |
|---|---|
| Pages (from-to) | 5731-5739 |
| Number of pages | 9 |
| Journal | Journal of Neuroscience |
| Volume | 28 |
| Issue number | 22 |
| DOIs | |
| State | Published - May 28 2008 |
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Keywords
- Action potential
- Ankyrin
- Cell adhesion molecule
- Juxtaparanode
- MAGUK
- Scaffold
ASJC Scopus subject areas
- Neuroscience(all)
- Medicine(all)
Cite this
Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2. / Ogawa, Yasuhiro; Horresh, Ido; Trimmer, James; Bredt, David S.; Peles, Elior; Rasband, Matthew N.
In: Journal of Neuroscience, Vol. 28, No. 22, 28.05.2008, p. 5731-5739.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Postsynaptic density-93 clusters Kv1 channels at axon initial segments independently of Caspr2
AU - Ogawa, Yasuhiro
AU - Horresh, Ido
AU - Trimmer, James
AU - Bredt, David S.
AU - Peles, Elior
AU - Rasband, Matthew N.
PY - 2008/5/28
Y1 - 2008/5/28
N2 - 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.
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.
KW - Action potential
KW - Ankyrin
KW - Cell adhesion molecule
KW - Juxtaparanode
KW - MAGUK
KW - Scaffold
UR - http://www.scopus.com/inward/record.url?scp=45949094424&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=45949094424&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.4431-07.2008
DO - 10.1523/JNEUROSCI.4431-07.2008
M3 - Article
C2 - 18509034
AN - SCOPUS:45949094424
VL - 28
SP - 5731
EP - 5739
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 22
ER -