2024
Leak channels from the iGluR superfamily
Here Sandra and Oksana dissect the glycine-binding domain of rat NMDA receptors and make an interesting discovery, also using non-canonical amino acids from our friend Hassan. This leads to a hypothesis that Yuhong tests in AKDF-type iGluRs from Trichoplax adhaerens, a simple little animal without a nervous system. We find that a single amino acid residue in the receptors’ ligand-binding domains profoundly controls channel activity. Full story readable/downloadable at Structure.
Neuropeptides in action
Our collaborators Valeria Kalienkova and Cristina Paulino, then in Groningen, have used cryo-EM to solve high-resolution structures of a worm neuropeptide-gated channel at rest, and in the presence of different neuropeptide ligands. The structures, together with complementary experimental dissection from Mowgli and Tim, show in high definition how neuropeptides like FMRFa activate excitatory currents in worm neurons. Full text freely available at NSMB.
Excitatory GABA receptors from the Delta iGluR family
Giulio, with help from Allan and others, shows that in numerous bilaterian animals, such as starfish, acorn worms, and aceol worms, delta-type glutamate receptor (delta iGluR) genes encode GABA-gated cation channels. This suggests that the classically inhibitory neurotransmitter GABA could also mediate excitatory signaling in numerous animals. Furthermore, this work uncovers the putative molecular basis by which vertebrate delta iGluRs became inactive, shedding some light on the mystery surrounding vertebrate delta iGluRs. Read the full text at PNAS here. Big thank you to ERC H2020 for funding.
2023
Photo credits: Andreas Hejnol and Aina Børve.
Hints about ION CHANNELs in early bilaterian Animals
Josep has worked with Aina Børve and Andreas Hejnol from UiB and Paul Bump from Stanford to dissect the evolution and function of acid-sensing ion channels (ASICs). We find that ASICs evolved in early bilaterians and were likely employed in peripheral roles before being deployed to the centralizing nervous system in the lineage to vertebrates. Josep also finds that some animals’ ASICs show very high pH sensitivity and sodium ion selectivity. The full version is now avaialble at eLife.
2022
Editors’s Pick at JBC! Neuropeptide-gated ion channels in spiralians and molecular determinants of ligand sensitivity.
Mowgli’s Ph.D. work characterizes neuropeptide-gated channels from various spiralian animals, uncovers their evolutionary relationships, and identifies amino acid residues that determine neuropeptide sensitivity. This work on invertebrate channels also offers hints on mammalian acid-sensing ion channel pharmacology, which Mowgli explores in experiments with acid-sensing ion channels. Thanks to Harald Hausen for some help with annelids. Full version at JBC.
Previous work
Via the link below, you will find some examples of ion channel evolution, pharmacology, and atomic mutagenesis in some of Tim’s previous work.