Unnexin is a protein subunit of a large-pore channel expressed by unicellular organisms

Author:

Güiza Juan1,Solís Francisco2,Valenzuela Bernardita2,Arancibia Duxan2,Zamorano Pedro2,González Jorge3,Saavedra Jonathan4,Neely Alan4ORCID,Salgado Magdiel4,Martínez Agustín D.4,Sáez Juan C.4,Vega José L.15

Affiliation:

1. Laboratory of Gap Junction Proteins and Parasitic Diseases (GaPaL), Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1240000, Chile

2. Laboratorio de Microorganismos Extremófilos, Instituto Antofagasta, Universidad de Antofagasta, Antofagasta 1240000, Chile

3. Departamento de Tecnología Médica, Unidad de Parasitología Molecular, Facultad Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1240000, Chile

4. Instituto de Neurociencias, Centro Interdisciplinario de Neurociencias de Valparaíso, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2381850, Chile

5. Departamento Biomédico, Facultad de Ciencias de la Salud, Universidad de Antofagasta, Antofagasta 1240000, Chile

Abstract

Cells of vertebrate and invertebrate organisms express proteins specialized in membrane channel–based cell–cell communication that are absent in unicellular organisms. We recently described the prediction of some members of the large-pore channel family in kinetoplastids, consisting of proteins called unnexins, which share several structural features with innexin and pannexin proteins. Here, we demonstrated that the 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. Low extracellular Ca 2+ /Mg 2+ levels or extracellular alkalinization, but not mechanical stretching, increases channel activity. The Unx1 channel mediates the influx of Ca 2+ 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 contains 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. Our data demonstrate that Unx1 forms large-pore membrane channels, 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. As morpholinos-induced downregulation of Unx1 reduces the infectivity of trypomastigotes, the Unx1 channels might be an attractive target for developing trypanocide drugs.

Funder

ANID | Fondo Nacional de Desarrollo Científico y Tecnológico

Agencia Nacional de Investigación y Desarrollo

Publisher

Proceedings of the National Academy of Sciences

Subject

Multidisciplinary

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