PhD Exit Seminar for Julia Gauberg (Senatore Lab)

Comparative Analysis of Ca_V1 and Ca_V2 Voltage-Gated Calcium Channels from Trichoplax adhaerens Reveals Early Divergence of Channel Types and Biophysical Properties

Abstract

To translate electrical signals into chemical signals at the synapse, cells employ voltage-gated calcium (Ca_V) channels. Most animals have three types of Ca_V channels, Ca_V1-Ca_V3, and of these, Ca_V1 and Ca_V2 channels have distinct roles at the synapse that are conserved across many animal phyla, from invertebrates to humans. Ca_V2 channels are involved in exocytosis of vesicles from the presynaptic cell, and Ca_V1 channels are typically involved in triggering gene transcription or contraction at the postsynaptic cell. Ca_V1 and Ca_V2 channels from nematodes to mammals have conserved features that are important for their post-/presynaptic functions, and it is possible that these features are conserved in more early-diverging animals as well. The most early-diverging animal phylum to have all three Ca_V channel homologues is the Placozoa. Placozoans are microscopic, marine animals that lack true tissues and synapses but still exhibit complex behaviours. Because they lack synapses but have all three types of Ca_V channels, they can be used as an evolutionary outgroup to examine the properties of Ca_V1 and Ca_V2 channels. The work presented in this thesis describes the characterization of the Ca_V1 and Ca_V2 channel homologues cloned from the placozoan Trichoplax adhaerens. The T. adhaerens Ca_V1 (TCa_V1) and Ca_V2 (TCa_V2) channels share structural and functional features that differentiate them from the TCa_V3 channel.  The biophysical properties of the TCa_V channels were found to be more similar to their mammalian homologues than each other. However, differences in modulation by cytosolic proteins such as G-proteins and calmodulin, which are defining features of these channels in mammals, are lacking in TCa_V1 and TCa_V2 channels. Thus, ancestral Ca_V1 and Cav2 channels likely diverged in their biophysical properties before gaining the ability to be modulated by different cytosolic proteins. Finally, TCa_V1 and TCa_V2 channel expression was examined in vivo, revealing that these channels are expressed in cell types that are known to be contractile and neuroendocrine-like. The differences in TCa_V1 and TCa_V2 expression suggests that they have different functions in vivo. Overall, this work provides invaluable insight into the properties of T. adhaerens Ca_V channels and contributes to our understanding of metazoan Ca_V channel evolution.

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Thursday, September 23rd, 2021 at 1:00 pm

Join Zoom Meeting

https://utoronto.zoom.us/j/84165975470

Meeting ID: 841 6597 5470

Host: Adriano Senatore (adriano.senatore@utoronto.ca)

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