Abstract
Voltage-gated potassium (Kv) channels comprise four transmembrane α subunits, often associated with cytoplasmic β subunits that impact channel expression and function. Here, we show that cell surface expression, voltage-dependent activation gating, and phosphorylation-dependent modulation of Kv2.1 are regulated by cytoplasmic N/C interaction within the α subunit. Kv2.1 surface expression is greatly reduced by C-terminal truncation. Tailless Kv2.1 channels exhibit altered voltage-dependent gating properties and lack the bulk of the phosphorylation-dependent modulation of channel gating. Remarkably, the soluble C terminus of Kv2.1 associates with tailless channels and rescues their expression, function, and phosphorylation-dependent modulation. Soluble N and C termini of Kv2.1 can also interact directly. We also show that the N/C-terminal interaction in Kv2.1 is governed by a 34 aa motif in the juxtamembrane cytoplasmic C terminus, and a 17 aa motif located in the N terminus at a position equivalent to the β subunit binding site in other Kv channels. Deletion of either motif disrupts N/C-terminal interaction and surface expression, function, and phosphorylation-dependent modulation of Kv2.1 channels. These findings provide novel insights into intrinsic mechanisms for the regulation of Kv2.1 trafficking, gating, and phosphorylation-dependent modulation through cytoplasmic N/C-terminal interaction, which resembles α/β subunit interaction in other Kv channels.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4982-4994 |
| Number of pages | 13 |
| Journal | Journal of Neuroscience |
| Volume | 28 |
| Issue number | 19 |
| DOIs | |
| State | Published - May 7 2008 |
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Keywords
- Assembly
- Electrophysiology
- Hippocampal neurons
- Immunocytochemistry
- Phosphorylation
- Potassium channel
ASJC Scopus subject areas
- Neuroscience(all)
- Medicine(all)
Cite this
Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel. / Mohapatra, Durga P.; Siino, Dominic F.; Trimmer, James.
In: Journal of Neuroscience, Vol. 28, No. 19, 07.05.2008, p. 4982-4994.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Interdomain cytoplasmic interactions govern the intracellular trafficking, gating, and modulation of the Kv2.1 channel
AU - Mohapatra, Durga P.
AU - Siino, Dominic F.
AU - Trimmer, James
PY - 2008/5/7
Y1 - 2008/5/7
N2 - Voltage-gated potassium (Kv) channels comprise four transmembrane α subunits, often associated with cytoplasmic β subunits that impact channel expression and function. Here, we show that cell surface expression, voltage-dependent activation gating, and phosphorylation-dependent modulation of Kv2.1 are regulated by cytoplasmic N/C interaction within the α subunit. Kv2.1 surface expression is greatly reduced by C-terminal truncation. Tailless Kv2.1 channels exhibit altered voltage-dependent gating properties and lack the bulk of the phosphorylation-dependent modulation of channel gating. Remarkably, the soluble C terminus of Kv2.1 associates with tailless channels and rescues their expression, function, and phosphorylation-dependent modulation. Soluble N and C termini of Kv2.1 can also interact directly. We also show that the N/C-terminal interaction in Kv2.1 is governed by a 34 aa motif in the juxtamembrane cytoplasmic C terminus, and a 17 aa motif located in the N terminus at a position equivalent to the β subunit binding site in other Kv channels. Deletion of either motif disrupts N/C-terminal interaction and surface expression, function, and phosphorylation-dependent modulation of Kv2.1 channels. These findings provide novel insights into intrinsic mechanisms for the regulation of Kv2.1 trafficking, gating, and phosphorylation-dependent modulation through cytoplasmic N/C-terminal interaction, which resembles α/β subunit interaction in other Kv channels.
AB - Voltage-gated potassium (Kv) channels comprise four transmembrane α subunits, often associated with cytoplasmic β subunits that impact channel expression and function. Here, we show that cell surface expression, voltage-dependent activation gating, and phosphorylation-dependent modulation of Kv2.1 are regulated by cytoplasmic N/C interaction within the α subunit. Kv2.1 surface expression is greatly reduced by C-terminal truncation. Tailless Kv2.1 channels exhibit altered voltage-dependent gating properties and lack the bulk of the phosphorylation-dependent modulation of channel gating. Remarkably, the soluble C terminus of Kv2.1 associates with tailless channels and rescues their expression, function, and phosphorylation-dependent modulation. Soluble N and C termini of Kv2.1 can also interact directly. We also show that the N/C-terminal interaction in Kv2.1 is governed by a 34 aa motif in the juxtamembrane cytoplasmic C terminus, and a 17 aa motif located in the N terminus at a position equivalent to the β subunit binding site in other Kv channels. Deletion of either motif disrupts N/C-terminal interaction and surface expression, function, and phosphorylation-dependent modulation of Kv2.1 channels. These findings provide novel insights into intrinsic mechanisms for the regulation of Kv2.1 trafficking, gating, and phosphorylation-dependent modulation through cytoplasmic N/C-terminal interaction, which resembles α/β subunit interaction in other Kv channels.
KW - Assembly
KW - Electrophysiology
KW - Hippocampal neurons
KW - Immunocytochemistry
KW - Phosphorylation
KW - Potassium channel
UR - http://www.scopus.com/inward/record.url?scp=44949210432&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=44949210432&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0186-08.2008
DO - 10.1523/JNEUROSCI.0186-08.2008
M3 - Article
C2 - 18463252
AN - SCOPUS:44949210432
VL - 28
SP - 4982
EP - 4994
JO - Journal of Neuroscience
JF - Journal of Neuroscience
SN - 0270-6474
IS - 19
ER -