K2P channels in plants and animals

Abstract

Two-pore domain potassium (K2P) channels are membrane proteins widely identified in mammals, plants, and other organisms. A functional channel is a dimer with each subunit comprising two pore-forming loops and four transmembrane domains. The genome of the model plant Arabidopsis thaliana harbors five genes coding for K2P channels. Homologs of Arabidopsis K2P channels have been found in all higher plants sequenced so far. As with the K2P channels in mammals, plant K2P channels are targets of external and internal stimuli, which fine-tune the electrical properties of the membrane for specialized transport and/or signaling tasks. Plant K2P channels are modulated by signaling molecules such as intracellular H(+) and calcium and physical factors like temperature and pressure. In this review, we ask the following: What are the similarities and differences between K2P channels in plants and animals in terms of their physiology? What is the nature of the last common ancestor (LCA) of these two groups of proteins? To answer these questions, we present physiological, structural, and phylogenetic evidence that discards the hypothesis proposing that the duplication and fusion that gave rise to the K2P channels occurred in a prokaryote LCA. Conversely, we argue that the K2P LCA was most likely a eukaryote organism. Consideration of plant and animal K2P channels in the same study is novel and likely to stimulate further exchange of ideas between students of these fields.

New Structures and Gating of Voltage-Dependent Potassium (Kv) Channels and Their Relatives: A Multi-Domain and Dynamic Question

“…This general architecture of the Kv channels is also shared by other S4-pore-loop/6TM1P channels (not all of them activated by voltage) with some subtle variations, including: (a) the addition of a fifth TM helix to the beginning of the VSD module in the large-conductance Ca 2+ -activated K + (BK) channel; (b) the almost total absence of positively charged residues in the S4 of some members of the family (e.g., some transient receptor potential or TRP channels); (c) the fusion of the four monomers in a single polypeptide in the voltage-gated Ca 2+ and Na + channels, where four similar repeats with six TMs mimic the tetrameric assembly of the Kv channels [4,5]. Finally, the concept of Kv channels being the result of an evolutive combination of two functionally autonomous VSD and PD modules [9,10,11] is reinforced by: (i) the existence of PD-only voltage-independent channels [12,13,14,15] that probably share a common ancestor with Kv and other voltage-dependent channels [11,16,17]; (ii) the demonstration of functional VSD-only-based voltage-dependent channels [18,19,20] and of voltage-controlled enzymes in which a VSD resembling those found in voltage-gated channels provides membrane potential control of the catalytic activity [21]; and (iii) the generation of voltage-gated ion channels by either fusing together VSDs and PDs from different sources [22,23,24], or co-expressing them as separate protein entities [25,26,27,28].…”

Functional characterization of Kv11.1 (hERG) potassium channels split in the voltage-sensing domain

“…VSD corresponds to transmembrane helices S1–S4, of which the primary voltage sensitive component is helix S4, containing the positively charged residues that move in response to changes in membrane potential [65]. The concept of Kv channels as a product of a evolutive combination of two functionally autonomous VSD and PD modules [2, 28, 69] is reinforced by (i) the existence of PD-only voltage-independent channels [8, 20, 27, 39] that probably share a common ancestor with Kv and other voltage-dependent channels [23, 29, 69], (ii) the demonstration of functional VSD-only-based voltage-dependent channels [10, 12, 54] and voltage-controlled enzymes in which a VSD resembling those found in voltage-gated channels provides membrane potential control of the catalytic activity [60] and (iii) the generation of voltage-gated ion channels by either fusing together VSDs and PDs from different sources [3, 33, 53] or co-expressing them as separate protein entities [14]. …”

A regulatory domain in the K2P2.1 (TREK-1) carboxyl-terminal allows for channel activation by monoterpenes

“…For example, while the activity of the Drosophila KCNK0 channel (K2P0) is enhanced by protein kinase phosphorylation (Zilberberg et al, 2000), removal of the C-terminal domain results in a channel that is insensitive to such activation (Cohen and Zilberberg, 2006;Zilberberg et al, 2000). The C-terminal domain of K2P2.1 channels was shown to be vital for regulation by phosphorylation Maingret et al, 2000), temperature (Bagriantsev et al, 2012;Maingret et al, 2000), arachidonic acid (Patel et al, 1998), internal acidification (Honore et al, 2002), internal lysophosphatidic acid (Gonzalez et al, 2015), PIP2 levels Woo et al, 2018) and mechanical stretch (Maingret et al, 1999). It was suggested that the proximal part of the Cterminal domain, which contains a charged region, is critical for chemical and mechanical activation of the channel (Patel et al, 1998).…”