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Alternative splicing modulates Kv channel clustering through a molecular ball and chain mechanism

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  • Nitzan Zandany

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Shir Marciano

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Elhanan Magidovich

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Teddy Frimerman

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Rinat Yehezkel

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Tzilhav Shem-Ad

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Limor Lewin

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Uri Abdu

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Irit Orr

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

  • Ofer Yifrach

    (Zlotowski Center for Neurosciences, Ben-Gurion University of the Negev)

Abstract

Ion channel clustering at the post-synaptic density serves a fundamental role in action potential generation and transmission. Here, we show that interaction between the Shaker Kv channel and the PSD-95 scaffold protein underlying channel clustering is modulated by the length of the intrinsically disordered C terminal channel tail. We further show that this tail functions as an entropic clock that times PSD-95 binding. We thus propose a ‘ball and chain’ mechanism to explain Kv channel binding to scaffold proteins, analogous to the mechanism describing channel fast inactivation. The physiological relevance of this mechanism is demonstrated in that alternative splicing of the Shaker channel gene to produce variants of distinct tail lengths resulted in differential channel cell surface expression levels and clustering metrics that correlate with differences in affinity of the variants for PSD-95. We suggest that modulating channel clustering by specific spatial-temporal spliced variant targeting serves a fundamental role in nervous system development and tuning.

Suggested Citation

  • Nitzan Zandany & Shir Marciano & Elhanan Magidovich & Teddy Frimerman & Rinat Yehezkel & Tzilhav Shem-Ad & Limor Lewin & Uri Abdu & Irit Orr & Ofer Yifrach, 2015. "Alternative splicing modulates Kv channel clustering through a molecular ball and chain mechanism," Nature Communications, Nature, vol. 6(1), pages 1-12, May.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms7488
    DOI: 10.1038/ncomms7488
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