CSB Departmental Seminar: “Evolution of voltage-gated Ca2+ and Degenerin/ENaC ion channel function in the Metazoa: Insights from the basal invertebrate Trichoplax adhaerens”

Ph.D Assistant Professor Adriano Senatore

Cell Systems and Biology, University of Toronto at UTM

“Evolution of voltage-gated Ca2+ and Degenerin/ENaC ion channel function in the Metazoa: Insights from the basal invertebrate Trichoplax adhaerens”

Abstract:

Trichoplax adhaerens is an early-diverging seawater animal that lacks muscle, synapses and a nervous system, and yet is capable of motile behaviors including feeding, phototaxis and chemotaxis. Transcriptome sequencing in our lab revealed that Trichoplax expresses a nearly full complement of genes required for fast and slow cellular signaling in the nervous system. Furthermore, recent work by ourselves and others indicates that Trichoplax uses small regulatory peptides, akin to neuropeptides, for coordinating some of its behaviors. In the Senatore lab, we seek to understand how certain genes with important roles in the nervous system evolved to take up their unique cellular functions. One area of interest are the voltage-gated calcium (CaV) channels, where in humans and most animals, CaV1 channels drive excitation-dependent muscle contraction, CaV2 drive pre-synaptic exocytosis, and CaV3 regulate the electrical properties of excitable cells. Evident from our transcriptome analysis, Trichoplax is the most early-diverging animal to posses all three types of metazoan CaV channels, despite lacking bona fide cell types where these channels are known to operate. Functionally, despite ~600 million years of divergence from other animal homologues, the cloned Trichoplax CaV channels exhibit core, defining electrophysiological/biophysical features when expressed in vitro. However, the channels lack protein-protein interaction motifs associated with their unique cellular localization and complexing. Indeed, the Trichoplax pre-synaptic CaV2 channel, which in vertebrate and invertebrate synapses interacts with pre-synaptic scaffolding proteins Mint1 and RIM, lacks the necessary motifs for these interactions. Instead, we have found that interactions between CaV2 channels and Mint1/RIM are conserved down to the Cnidaria (jellyfish, sea anemones and corals), representing an apparent key adaptation for CaV2 channel localization and function in the evolving synapse. A second area of interest to us are the Degenerin/ENaC family of sodium channels (DEG/ENaC), which have undergone significant evolutionary change and genetic expansion in distinct animal lineages. This has resulted in highly variable gating mechanisms, ranging from activation by extracellular protons (i.e. acid-activated or ASIC channels), neuropeptides (peptide-gated channels) or mechanical stress. In humans, DEG/ENaC channels are essential for epithelial Na+ re-uptake in the kidney epithelium (ENaC channels), for synaptic plasticity and ischemia in the brain (ASIC channels), and for nociception in the periphery (ASIC channels). Altogether, the rapid evolution observed within this family has made it difficult to infer the core properties of the ancestral DEG/ENaC channel, and further, to envision how the different modalities of gating evolved at a mechanistic, functional level. Through work on cloned Trichoplax DEG/ENaC channel homologues, we have made some interesting findings that help infer the ancestral properties of DEG/ENaC channels. Furthermore, we have discovered a set of acid-activated channels (ASIC-like), previously thought to only exist in chordates and other deuterostome animals, that lack key amino acid determinants and hence evolved this gating capacity independently.

Friday, Oct 4th, 2019

11:00 a.m

Ramsay Wright, 432

Host: Arneet Saltzman: arneet.saltzman@utoronto.ca