In the adult retina, we have previously shown that Nogo-A was highly expressed in
Müller glia. However, the role of Nogo-A in the glial cell physiology is not clear.
In this study, we investigated the possible influence that Nogo-A may exert on other
polarized molecules in Müller cells, in particular inwardly rectifying potassium channel
4.1 (Kir4.1) and aquaporin 4 (AQP4) that respectively control potassium and water
exchange in glial cells. Our results showed that adenovirus-mediated Nogo-A overexpression
with AdNogo-A increased the immunofluorescent signal of Kir4.1 in rat Müller cell
line 1 (rMC-1) cells but did not change its expression level by Western blotting.
In vivo, AdNogo-A induced ectopic Kir4.1 immunoreactivity throughout the radial processes
of Müller cells compared with AdLacZ control virus. Surprisingly, AdNogo-A did not
modify the distribution of Dp71 and AQP4 that are common binding partners for Kir4.1
in the dystrophin-associated protein (DAP) complex anchored at the plasma membrane
of Müller glia. Immunoprecipitation experiments revealed molecular interactions between
Nogo-A and Kir4.1. In Nogo-A KO mouse retinae, the distribution of Kir4.1 was not
different from that observed in Wild-Type (WT) animals. In addition, potassium conductance
did not change in freshly dissociated Nogo-A KO Müller glia compared with WT cells.
In summary, the increase of Nogo-A expression can selectively influence the distribution
of Kir4.1 in glia but is not essential for Kir4.1-mediated potassium conductance at
the plasma membrane in physiological conditions. Nogo-A-Kir4.1 interactions may, however,
contribute to pathological processes taking place in the retina, for instance, after