Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway

Research output: Contribution to journalJournal articleResearchpeer-review

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Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway. / Jensen, Camilla Stampe; Watanabe, Shoji; Stas, Jeroen Ingrid; Klaphaak, Jessica; Yamane, Ayaka; Schmitt, Nicole; Olesen, Søren-Peter; Trimmer, James S; Rasmussen, Hanne Borger; Misonou, Hiroaki.

In: The Journal of neuroscience : the official journal of the Society for Neuroscience, Vol. 37, No. 48, 29.11.2017, p. 11523-11536.

Research output: Contribution to journalJournal articleResearchpeer-review

Harvard

Jensen, CS, Watanabe, S, Stas, JI, Klaphaak, J, Yamane, A, Schmitt, N, Olesen, S-P, Trimmer, JS, Rasmussen, HB & Misonou, H 2017, 'Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway', The Journal of neuroscience : the official journal of the Society for Neuroscience, vol. 37, no. 48, pp. 11523-11536. https://doi.org/10.1523/JNEUROSCI.3510-16.2017

APA

Jensen, C. S., Watanabe, S., Stas, J. I., Klaphaak, J., Yamane, A., Schmitt, N., ... Misonou, H. (2017). Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience, 37(48), 11523-11536. https://doi.org/10.1523/JNEUROSCI.3510-16.2017

Vancouver

Jensen CS, Watanabe S, Stas JI, Klaphaak J, Yamane A, Schmitt N et al. Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway. The Journal of neuroscience : the official journal of the Society for Neuroscience. 2017 Nov 29;37(48):11523-11536. https://doi.org/10.1523/JNEUROSCI.3510-16.2017

Author

Jensen, Camilla Stampe ; Watanabe, Shoji ; Stas, Jeroen Ingrid ; Klaphaak, Jessica ; Yamane, Ayaka ; Schmitt, Nicole ; Olesen, Søren-Peter ; Trimmer, James S ; Rasmussen, Hanne Borger ; Misonou, Hiroaki. / Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway. In: The Journal of neuroscience : the official journal of the Society for Neuroscience. 2017 ; Vol. 37, No. 48. pp. 11523-11536.

Bibtex

@article{19bd84423b5b405baf8ce46733f43ea0,
title = "Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway",
abstract = "Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface clusters in the soma and proximal dendrites as well as in the axon initial segment (AIS). Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching imaging, mutagenesis, and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted and clustered localization in the AIS. These results indicate that neurons can regulate the expression and clustering of Kv2.1 in different membrane domains independently by using two distinct localization mechanisms, which would allow neurons to precisely control local membrane excitability.SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including putative phosphorylation sites, that is important for the AIS localization. This raises the possibility that the destination of a channel protein can be dynamically regulated via changes in post-translational modification, which would impact the excitability of specific membrane compartments.",
keywords = "Animals, Axon Initial Segment, Cell Membrane, Cells, Cultured, Female, HEK293 Cells, Hippocampus, Humans, Male, Neurons, Protein Transport, Rats, Secretory Pathway, Shab Potassium Channels, Journal Article",
author = "Jensen, {Camilla Stampe} and Shoji Watanabe and Stas, {Jeroen Ingrid} and Jessica Klaphaak and Ayaka Yamane and Nicole Schmitt and S{\o}ren-Peter Olesen and Trimmer, {James S} and Rasmussen, {Hanne Borger} and Hiroaki Misonou",
note = "Copyright {\circledC} 2017 the authors 0270-6474/17/3711523-14$15.00/0.",
year = "2017",
month = "11",
day = "29",
doi = "10.1523/JNEUROSCI.3510-16.2017",
language = "English",
volume = "37",
pages = "11523--11536",
journal = "The Journal of neuroscience : the official journal of the Society for Neuroscience",
issn = "0270-6474",
publisher = "Society for Neuroscience",
number = "48",

}

RIS

TY - JOUR

T1 - Trafficking of Kv2.1 Channels to the Axon Initial Segment by a Novel Nonconventional Secretory Pathway

AU - Jensen, Camilla Stampe

AU - Watanabe, Shoji

AU - Stas, Jeroen Ingrid

AU - Klaphaak, Jessica

AU - Yamane, Ayaka

AU - Schmitt, Nicole

AU - Olesen, Søren-Peter

AU - Trimmer, James S

AU - Rasmussen, Hanne Borger

AU - Misonou, Hiroaki

N1 - Copyright © 2017 the authors 0270-6474/17/3711523-14$15.00/0.

PY - 2017/11/29

Y1 - 2017/11/29

N2 - Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface clusters in the soma and proximal dendrites as well as in the axon initial segment (AIS). Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching imaging, mutagenesis, and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted and clustered localization in the AIS. These results indicate that neurons can regulate the expression and clustering of Kv2.1 in different membrane domains independently by using two distinct localization mechanisms, which would allow neurons to precisely control local membrane excitability.SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including putative phosphorylation sites, that is important for the AIS localization. This raises the possibility that the destination of a channel protein can be dynamically regulated via changes in post-translational modification, which would impact the excitability of specific membrane compartments.

AB - Kv2.1 is a major delayed-rectifier voltage-gated potassium channel widely expressed in neurons of the CNS. Kv2.1 localizes in high-density cell-surface clusters in the soma and proximal dendrites as well as in the axon initial segment (AIS). Given the crucial roles of both of these compartments in integrating signal input and then generating output, this localization of Kv2.1 is ideal for regulating the overall excitability of neurons. Here we used fluorescence recovery after photobleaching imaging, mutagenesis, and pharmacological interventions to investigate the molecular mechanisms that control the localization of Kv2.1 in these two different membrane compartments in cultured rat hippocampal neurons of mixed sex. Our data uncover a unique ability of Kv2.1 channels to use two molecularly distinct trafficking pathways to accomplish this. Somatodendritic Kv2.1 channels are targeted by the conventional secretory pathway, whereas axonal Kv2.1 channels are targeted by a nonconventional trafficking pathway independent of the Golgi apparatus. We further identified a new AIS trafficking motif in the C-terminus of Kv2.1, and show that putative phosphorylation sites in this region are critical for the restricted and clustered localization in the AIS. These results indicate that neurons can regulate the expression and clustering of Kv2.1 in different membrane domains independently by using two distinct localization mechanisms, which would allow neurons to precisely control local membrane excitability.SIGNIFICANCE STATEMENT Our study uncovered a novel mechanism that targets the Kv2.1 voltage-gated potassium channel to two distinct trafficking pathways and two distinct subcellular destinations: the somatodendritic plasma membrane and that of the axon initial segment. We also identified a distinct motif, including putative phosphorylation sites, that is important for the AIS localization. This raises the possibility that the destination of a channel protein can be dynamically regulated via changes in post-translational modification, which would impact the excitability of specific membrane compartments.

KW - Animals

KW - Axon Initial Segment

KW - Cell Membrane

KW - Cells, Cultured

KW - Female

KW - HEK293 Cells

KW - Hippocampus

KW - Humans

KW - Male

KW - Neurons

KW - Protein Transport

KW - Rats

KW - Secretory Pathway

KW - Shab Potassium Channels

KW - Journal Article

U2 - 10.1523/JNEUROSCI.3510-16.2017

DO - 10.1523/JNEUROSCI.3510-16.2017

M3 - Journal article

VL - 37

SP - 11523

EP - 11536

JO - The Journal of neuroscience : the official journal of the Society for Neuroscience

JF - The Journal of neuroscience : the official journal of the Society for Neuroscience

SN - 0270-6474

IS - 48

ER -

ID: 189625068