Affiliation:
1. Department of Life Sciences, School of Brain Sciences and Cognition, Ben-Gurion University of the Negev, P.O. Box 653, Beer Sheva 84105, Israel
Abstract
In recent years, it has become clear that intrinsically disordered protein segments play diverse functional roles in many cellular processes, thus leading to a reassessment of the classical structure–function paradigm. One class of intrinsically disordered protein segments is entropic clocks, corresponding to unstructured random protein chains involved in timing cellular processes. Such clocks were shown to modulate ion channel processes underlying action potential generation, propagation, and transmission. In this review, we survey the role of entropic clocks in timing intra- and inter-molecular binding events of voltage-activated potassium channels involved in gating and clustering processes, respectively, and where both are known to occur according to a similar ‘ball and chain’ mechanism. We begin by delineating the thermodynamic and timing signatures of a ‘ball and chain’-based binding mechanism involving entropic clocks, followed by a detailed analysis of the use of such a mechanism in the prototypical Shaker voltage-activated K+ channel model protein, with particular emphasis on ion channel clustering. We demonstrate how ‘chain’-level alternative splicing of the Kv channel gene modulates entropic clock-based ‘ball and chain’ inactivation and clustering channel functions. As such, the Kv channel model system exemplifies how linkage between alternative splicing and intrinsic disorder enables the functional diversity underlying changes in electrical signaling.
Funder
Israel Science Foundation
Subject
General Physics and Astronomy
Reference56 articles.
1. Kandel, E.R., Schwartz, J.H., Jessell, T.M., Siegelbaum, S.A., and Hudspeth, A.J. (2000). Principles of Neural Science, McGraw-Hill. [4th ed.].
2. The Distribution and Targeting of Neuronal Voltage-Gated Ion Channels;Lai;Nat. Rev. Neurosci.,2006
3. Subcellular Localization of K+ Channels in Mammalian Brain Neurons: Remarkable Precision in the Midst of Extraordinary Complexity;Trimmer;Neuron,2015
4. Action-Potential Propagation Gated by an Axonal IA-like K+ Conductance in Hippocampus;Debanne;Nature,1997
5. Reduced K+ Channel Inactivation, Spike Broadening, and after- Hyperpolarization in KvB1.1-Deficient Mice with Impaired Learning;Giese;Learn. Mem.,1998