1.A.138.  The Unnexin (Unx) Family 

Cells of vertebrates and invertebrates express proteins specialized in membrane channel-based cell-cell communication that are absent in unicellular organisms. Members of the large-pore channel family in kinetoplastids, consisting of proteins called unnexins (Unx's) which share several structural features with innexins.  Güiza et al. 2023 demonstrated that a unnexin1 protein (Unx1) is delivered to the cell membrane, displaying a topology consisting of four transmembrane domains with C and N termini on the cytoplasmic side and form large-pore channels that are permeable to small molecules including Ca²⁺ and DAPI. Low extracellular Ca²⁺/Mg²⁺ levels or extracellular alkalinization, but not mechanical stretching, increases channel activity. The Unx1 channel mediates the influx of Ca²⁺ and does not form intercellular dye coupling between HeLa Unx1 transfected cells. Unx1 channel function was further evidenced by its ability to mediate ionic currents when expressed in Xenopus oocytes. Downregulation of Unx1 mRNA with morpholine inhibited Trypanosoma cruzi invasion. Phylogenetic analysis revealed the presence of Unx1 homologs in other protozoan parasites, suggesting a conserved function for these channel parasites in other protists. Thus, Unx1 forms large-pore membrane channels (hemichannels but not gap junctions), which may serve as a diffusional pathway for ions and small molecules that are likely to be metabolic substrates or waste products, and signaling autocrine and paracrine molecules that could be involved in cell invasion (Güiza et al. 2023). This family may show sequence similarity and topology with TC family 1.A.101 as well as the Innexin family (TC# 1.A.25)