Multiple Domains in the Kv7.3 C-Terminus Can Regulate Localization to the Axon Initial Segment
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Multiple Domains in the Kv7.3 C-Terminus Can Regulate Localization to the Axon Initial Segment. / Hefting, Louise Leth; D'Este, Elisa; Arvedsen, Emil; Benned-Jensen, Tau; Rasmussen, Hanne Borger.
I: Frontiers in Cellular Neuroscience, Bind 14, 10, 2020.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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TY - JOUR
T1 - Multiple Domains in the Kv7.3 C-Terminus Can Regulate Localization to the Axon Initial Segment
AU - Hefting, Louise Leth
AU - D'Este, Elisa
AU - Arvedsen, Emil
AU - Benned-Jensen, Tau
AU - Rasmussen, Hanne Borger
PY - 2020
Y1 - 2020
N2 - The voltage-gated Kv7.2/Kv7.3 potassium channel is a critical regulator of neuronal excitability. It is strategically positioned at the axon initial segment (AIS) of neurons, where it effectively inhibits repetitive action potential firing. While the selective accumulation of Kv7.2/Kv7.3 channels at the AIS requires binding to the adaptor protein ankyrin G, it is currently unknown if additional molecular mechanisms contribute to the localization and fine-tuning of channel numbers at the AIS. Here, we utilized a chimeric approach to pinpoint regions within the Kv7.3 C-terminal tail with an impact upon AIS localization. This strategy identified two domains with opposing effects upon the AIS localization of Kv7.3 chimeras expressed in cultured hippocampal neurons. While a membrane proximal domain reduced AIS localization of Kv7.3 chimeras, helix D increased and stabilized chimera AIS localization. None of the identified domains were required for AIS localization. However, the domains modulated the relative efficiency of the localization raising the possibility that the two domains contribute to the regulation of Kv7 channel numbers and nanoscale organization at the AIS.
AB - The voltage-gated Kv7.2/Kv7.3 potassium channel is a critical regulator of neuronal excitability. It is strategically positioned at the axon initial segment (AIS) of neurons, where it effectively inhibits repetitive action potential firing. While the selective accumulation of Kv7.2/Kv7.3 channels at the AIS requires binding to the adaptor protein ankyrin G, it is currently unknown if additional molecular mechanisms contribute to the localization and fine-tuning of channel numbers at the AIS. Here, we utilized a chimeric approach to pinpoint regions within the Kv7.3 C-terminal tail with an impact upon AIS localization. This strategy identified two domains with opposing effects upon the AIS localization of Kv7.3 chimeras expressed in cultured hippocampal neurons. While a membrane proximal domain reduced AIS localization of Kv7.3 chimeras, helix D increased and stabilized chimera AIS localization. None of the identified domains were required for AIS localization. However, the domains modulated the relative efficiency of the localization raising the possibility that the two domains contribute to the regulation of Kv7 channel numbers and nanoscale organization at the AIS.
KW - ankyrin-G
KW - hippocampal neurons
KW - Kv7
KW - KCNQ
KW - FRAP
KW - double-FRAP
KW - STED
KW - nanoscopy
U2 - 10.3389/fncel.2020.00010
DO - 10.3389/fncel.2020.00010
M3 - Journal article
C2 - 32116557
VL - 14
JO - Frontiers in Cellular Neuroscience
JF - Frontiers in Cellular Neuroscience
SN - 1662-5102
M1 - 10
ER -
ID: 237417019