External Cd2+ and protons activate the hyperpolarization-gated K+ channel KAT1 at the voltage sensor J Gen Physiol (2021) 153 (1): e202012647. https://doi.org/10.1085/jgp.202012647
Yunqing’s first paper showing that plant and animal CNBD superfamily ion channels adopt similar voltage sensor structures in the down state at hyperpolarized voltages. Both have divalent and proton bindind sites in the external voltage sensor in the down state. Interestingly, KAT1 is a hyperpolarization-gated channel so divalents and protons, which inhibit activation of animal EAG family K+ channels, activate it. A big question in the field is understanding why these similar voltage sensor conformations oppositely influence pore opening in depolarization- and hyperpolarization-gated channels. We also thought it was cool that the plant channel KAT1 responds to a much lower pH range than animal EAG channels; plants typically have low extracellular pH compared to animals. Both channel types seems tuned to respond to the pH range found in their native environment.
Cytoskeletal and synaptic polarity of LWamide-like+ ganglion neurons in the sea anemone Nematostella vectensis. J Exp Biol, 2020 Nov 10;223(Pt 21):jeb233197. https://journals.biologists.com/jeb/article/223/21/jeb233197/226253
One of the big questions in evolutionary neurobiology is figuring out how and when functional neuronal polarity evolved. In particular, we want to know whether functionally distinct axons and dendrites predate the evolution of polarized nervous systems in bilaterian animals. We have been developing the sea anemone Nematostella vectensis to address this question. Cnidarians like Nematostella are cousins to bilaterians, but split off when nervous systems were still comparatively simple diffuse nets. This is Michelle’s paper showing that a major characteristic type of the cnidarian nerve net is non-polar and has axon-like processes that likely signal bidirectionally. We don’t think that is the end of the story however, so stay tuned – there may be other cell types that point to a more complex story in which at least some important aspects of neuronal polarity evolved in early nerve nets. We are particularly proud of this paper because it took years to develop the tools we needed to enable live imaging of transgenic sea anemones.
The S6 gate in regulatory Kv6 subunits restricts heteromeric K+ channel stoichiometry http://jgp.rupress.org/content/150/12/1702
This paper was the core of Aditya’s thesis and is a great example of how you can use evolution to highlight key features of proteins. K+ channels are tetrameric and can typically form as homotetramers composed of four identical subunits. However, some subunits have evolved a “regulatory” phenotype in which they can no longer make homotetramers and instead depend on mixing with other closely-related K+ channel subunits to form functional channels, often in an unusual asymmetric 3:1 ratio. We identified sequence changes that correlated with evolution of the regulatory phenotype and found that the interface between subunits in the lining of the pore itself played a key role in determining channel composition. Previously, it had been thought that a cytoplasmic sorting domain, T1, was fully responsible for channel subunit composition. We proposed a two-step model of how you can evolve asymmetric channels that involves sequential mutation of T1 and the pore. This is one of those typical JGP papers with heroically complicated biophysics experiments. We also received a great assist from the Hancock lab who worked with us to count subunits in individual channels using fluorescent tags.
Evolution and Structural Characteristics of Plant Voltage-Gated K+ Channels http://www.plantcell.org/content/early/2018/11/01/tpc.18.00523
This a review Greg and I wrote with Sally on the evolution of Plant Voltage-Gated K+ channels and the CNBD channel superfamily to which they belong. We managed to squeeze a lot of new analyses into it, so its sort of a hybrid review/research article. Here is my favorite thing in the article: 1) CNBD superfamily channels, which include the plant channels and a wide range of animal channels that control sensory perception, neuronal excitability and heartbeat, come from a prokaryotic ancestor that is common in eubacterial lineages but appears to be absent (at least so far) in the Archaea. Since eukaryotes evolved from the Archaeal lineage, that could mean we picked up the CNBD channel superfamily by lateral gene transfer. There of course are plenty of documented cases of lateral gene transfer, but I still think its amazing that the channels that we use to see and smell and the channels that plants depend on to open and close their leaf pores may have been “borrowed” from bacteria. The Plant Cell is of course nothing new to Sally, but it was nice for me to bag another top journal for my “life list”.