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

Nitzan Zandany, Shir Marciano, Elhanan Magidovich, Teddy Frimerman, Rinat Yehezkel, Tzilhav Shem-Ad, Limor Lewin, Uri Abdu, Irit Orr, Ofer Yifrach

Research output: Contribution to journalArticlepeer-review

18 Scopus citations


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.

Original languageEnglish
Article number6488
JournalNature Communications
StatePublished - 1 Jan 2015

ASJC Scopus subject areas

  • Chemistry (all)
  • Biochemistry, Genetics and Molecular Biology (all)
  • Physics and Astronomy (all)


Dive into the research topics of 'Alternative splicing modulates Kv channel clustering through a molecular ball and chain mechanism'. Together they form a unique fingerprint.

Cite this