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Browsing Biology by Author "Anna Yuriyivna Kotova"
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Item Open Access Molecular Mechanisms Underlying Regulation and Function of Neuronal Gap Junction Proteins: Connexin 36 and Connexin 27.5.(2022-12-14) Kotova, Anna Yuriyivna; Zoidl, Georg R.Electrical synapses, known as gap junctions, are critical to neuronal synchronization and signal transmission. Gap junctions are composed of two docked hemichannels, each consisting of single protein subunits called connexins. Regulation and function of connexins are vital for the plasticity of the electrical synapses. Connexin regulation is dependent on their interacting partners as they affect turnover and channel properties. Here we explored the functional relevance of the interaction between mouse Connexin 36 (Cx36), major neuronal connexin, and mouse Caveolin-1 (Cav-1) in the Neuro 2a cell line. Cav-1 is known to mediate the endocytosis of membrane proteins, therefore its role in trafficking of Cx36 was explored. Together results showed that Cx36/Cav-1 interaction selects for the rapid calcium and caveolin dependent endocytosis and is critical for the internalization of Cx36. Another means for regulating connexin function is through their ability to oligomerize with different connexin isoforms to form heteromeric and heterotypic channels. The oligomerization capabilities between zebrafish Cx35b, an orthologue of mouse Cx36, and a novel zebrafish connexin, Cx27.5, were explored in Neuro 2a cells. The co-localization of Cx36/35b and Cx27.5 was also investigated in the zebrafish retina, as its high organization allows to study the gap junction connections between different cell types. Data showed that oligomerization of Cx35b and Cx27.5 led to a formation of distinct channels which potentially allow for specialized intercellular connection between different cell types. Cx27.5 is a novel connexin, and its functional relevance remains unknown. Previously reported expression in the zebrafish retina and co-localization with Cx36/35b further reinforced the hypothesis that the Cx27.5 function could be critical for visual processing. The protein and mRNA expression profile of Cx27.5 showed high expression in the brain and retina, specifically, the inner plexiform layer. By employing a Cx27.5 knock-out zebrafish line, the role of Cx27.5 in visual processing was investigated. The results proved Cx27.5 to be an essential player in the signal transmission and network connectivity of the zebrafish retina, as well as the perception of directional motion. In summary, the findings in this thesis describe the multifaced molecular mechanisms that underlie the function and regulation of neuronal connexins.