Human GluR6c, a functional splicing variants of GluR6, is mainly expressed in non-nervous cells

Kainate-type glutamate receptors (KARs) are receptor channels with a variety of distinct physiological functions in synaptic transmission, depending on their sub-cellular location in functional neuronal compartments. The kainate receptor subunit GluR6 presents different splice variants involving the C-terminal domain, namely GluR6a, GluR6b and GluR6c. In this study, we report the analysis of the three human splicing isoforms and in particular of the uncharacterized hGluR6c. When expressed in COS-7 cells, hGluR6a receptor subunit was highly present on the surface of the plasma membrane, whereas hGluR6b and hGluRc were poorly transported to the membrane. Electrophysiological studies of homomeric receptors showed that hGluR6c subunit can generate functional receptors with characteristics similar to the GluR6b variant. mRNA expression analysis demonstrated that hGluR6c variant is mainly expressed in non-neuronal cells and barely expressed in neuronal ones. Interestingly, undifferentiated NT2 cells expressing only the hGluR6c isoform, during neuronal differentiation induced by retinoic acid, increased the expression level of the neuronal form hGluR6a with a parallel decreased of hGluR6c. Overall, our data indicate that hGluR6c might have unique properties in non-nervous cells and in the first stages of CNS development.