Trafficking of Kv2.1 channels to the axon initial segment by a novel nonconventional secretory pathway

Camilla Stampe Jensen, Shoji Watanabe, Jeroen Ingrid Stas, Jessica Klaphaak, Ayaka Yamane, Nicole Schmitt, Søren Peter Olesen, James Trimmer, Hanne Borger Rasmussen, Hiroaki Misonou

Research output: Contribution to journalArticle

22 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)11523-11536
Number of pages14
JournalJournal of Neuroscience
Volume37
Issue number48
DOIs
StatePublished - Nov 29 2017

Keywords

  • Excitability
  • Phosphorylation
  • Potassium channel
  • Sorting
  • Targeting

ASJC Scopus subject areas

  • Neuroscience(all)

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    Stampe Jensen, C., Watanabe, S., Stas, J. I., Klaphaak, J., Yamane, A., Schmitt, N., Olesen, S. P., Trimmer, J., Rasmussen, H. B., & Misonou, H. (2017). Trafficking of Kv2.1 channels to the axon initial segment by a novel nonconventional secretory pathway. Journal of Neuroscience, 37(48), 11523-11536. https://doi.org/10.1523/JNEUROSCI.3510-16.2017