Biology subjects

Mayorova, T. D.

Publications and source records attributed to Mayorova, T. D..

4 recordsLinked to original sources

bioRxiv2025

Functional and phylogenetic analysis of placozoan GPCRs reveal the prebilaterian origin of monoaminergic signalling.

Monoamines are biologically active compounds crucial for neurotransmission and various physiological processes. They include neurotransmitters like serotonin, dopamine, and melatonin, which regulate mood, movement, and sleep in humans. In ecdysozoans, monoamines such as tyramine are important for modulating locomotion, learning, and feeding. The monoaminergic signalling system has been considered a bilaterian innovation, with conflicting evidence supporting its existence in earlier branching, non-bilaterian animals. Here, we challenge the bilaterian origin hypothesis by combining large-scale receptor deorphanisation with phylogenetic analyses to identify monoamine receptors from the placozoan Trichoplax adhaerens. We demonstrate that these receptors are homologous to known bilaterian GPCRs, and behavioural assays demonstrate that monoamines like tyramine and tryptamine affect the speed of locomotion and body shape of this animal, respectively. These responses, together with the presence of biosynthetic enzymes for these molecules, reveal that monoaminergic signalling is both active and endogenous in placozoans. Our findings provide compelling evidence for a prebilaterian origin of monoaminergic systems, reshaping our understanding of early nervous system evolution.

evolutionary biology↗

bioRxiv2025

NALCN/Cch1 channelosome subunits originated in early eukaryotes and are fully conserved in animals, fungi, and apusomonads

The sodium leak channel NALCN, a key regulator of neuronal excitability, associates with three ancillary subunits that are critical for its function: an extracellular subunit called FAM155, and two cytoplasmic subunits called UNC79 and UNC80. Interestingly, NALCN and FAM155 have orthologous phylogenetic relationships with the fungal calcium channel Cch1 and its extracellular subunit Mid1, however, UNC79 and UNC80 have not been reported outside of animals. In this study, we leveraged expanded gene sequence data available for eukaryotes to re-examine the evolutionary origins of NALCN and Cch1 channel subunits. Our analysis corroborates the direct phylogenetic relationship between NALCN and Cch1 and identifies a larger clade of related channels in additional eukaryotic taxa. We also identify homologues of FAM155/Mid1 in Cryptista algae, and UNC79 and UNC80 homologues in numerous non-metazoan eukaryotes including basidiomycete and mucoromycete fungi, and the microbial eukaryotic taxa Apusomonadida, Malawimonadida, and Discoba. Furthermore, we find that most major animal lineages, except ctenophores, possess a full complement of NALCN subunits. Comparing structural predictions with the solved structure of the human NALCN complex supports orthologous relationships between metazoan and non-metazoan FAM155/Mid1, UNC79, and UNC80 homologues. Together, our analyses reveal unexpected diversity and ancient eukaryotic origins of NALCN/Cch1 channelosome subunits and raise interesting questions about the functional nature of this conserved channel complex within a broad, eukaryotic context.

evolutionary biology↗

bioRxiv2024

Placozoan secretory cell types implicated in feeding, innate immunity and regulation of behavior

Placozoa are millimeter-sized, flat, irregularly shaped ciliated animals that crawl on surfaces in warm oceans feeding on biofilms, which they digest externally. They stand out from other animals due to their simple body plans. They lack organs, body cavities, muscles and a nervous system and have only seven broadly defined morphological cell types, each with a unique distribution. Analyses of single cell transcriptomes of four species of placozoans revealed greater diversity of secretory cell types than evident from morphological studies, but the locations of many of these new cell types were unknown and it was unclear which morphological cell types they represent. Furthermore, there were contradictions between the conclusions of previous studies and the single cell RNAseq studies. To address these issues, we used mRNA probes for genes encoding secretory products expressed in different metacells in Trichoplax adhaerens to localize cells in whole mounts and in dissociated cell cultures, where their morphological features could be visualized and identified. The nature and functions of their secretory granules were further investigated with electron microscopic techniques and by imaging secretion in live animals during feeding episodes. We found that two cell types participate in disintegrating prey, one resembling a lytic cell type in mammals and another combining features of zymogen gland cells and enterocytes. We identified secretory epithelial cells expressing glycoproteins or short peptides implicated in defense. We located seven peptidergic cell types and two types of mucocytes. Our findings reveal mechanisms that placozoans use to feed and protect themselves from pathogens and clues about neuropeptidergic signaling. We compare placozoan secretory cell types with cell types in other animal phyla to gain insight about general evolutionary trends in cell type diversification, as well as pathways leading to the emergence of synapomorphies.

evolutionary biology↗

bioRxiv2022

Function and phylogeny support the independent evolution of acid-sensing ion channels in the Placozoa

Acid-sensing ion channels (ASICs) are proton-gated cation channels that are part of the Deg/ENaC ion channel family, which also includes neuropeptide-, bile acid-, and mechanically-gated channels. Despite sharing common tertiary and quaternary structures, strong sequence divergence within the Deg/ENaC family has made it difficult to resolve their phylogenetic relationships, and by extension, whether channels with common functional features, such as proton-activation, share common ancestry or evolved independently. Here, we report that a Deg/ENaC channel from the early diverging placozoan species Trichoplax adhaerens, named TadNaC2, conducts proton-activated currents in vitro with biophysical features that resemble those of the mammalian ASIC1 to ASIC3 channels. Through a combined cluster- based and phylogenetic analysis, we successfully resolve the evolutionary relationships of most major lineages of metazoan Deg/ENaC channels, identifying two subfamilies within the larger Deg/ENaC family that are of ancient, pre-bilaterian origin. We also identify bona fide Deg/ENaC channel homologues from filasterean and heterokont single celled eukaryotes. Furthermore, we find that ASIC channels, TadNaC2, and various other proton-activated channels from vertebrates and invertebrates are part of phylogenetically distinct lineages. Through structural modelling and mutation analysis, we find that TadNaC2 proton-activation employs fundamentally different molecular determinants than ASIC channels, and identify two unique histidine residues in the placozoan channel that are required for its proton-activation. Together, our phylogenetic and functional analyses support the independent evolution of proton-activated channels in the phylum Placozoa. Spurred by our discovery of pH sensitive channels, we discovered that despite lacking a nervous system, Trichoplax can sense changes in extracellular pH to coordinate its various cell types to locomote away from acidic environments, and to contract upon rapid exposure to acidic pH in a Ca2+-dependent manner. Lastly, via yeast 2 hybrid screening, we find that the Trichoplax channels TadNaC2 and TadNaC10, belonging to the two separate Deg/ENaC subfamilies, interact with the cytoskeleton organizing protein filamin, similar to the interaction reported for the human ENaC channels.

evolutionary biology↗