RT Journal Article SR Electronic T1 The IgCAM BT-IgSF (IgSF11) is essential for connexin43-mediated astrocyte-astrocyte and ependymal cell-cell coupling JF bioRxiv FD Cold Spring Harbor Laboratory SP 2022.06.17.496568 DO 10.1101/2022.06.17.496568 A1 Laura Pelz A1 Laura Dossou A1 Nine Kompier A1 René Jüttner A1 Gabrielle Siemonsmeier A1 Niklas Meyer A1 Elijah D. Lowenstein A1 Ines Lahmann A1 Helmut Kettenmann A1 Carmen Birchmeier A1 Fritz G. Rathjen YR 2022 UL http://biorxiv.org/content/early/2022/06/17/2022.06.17.496568.abstract AB The type I transmembrane protein BT-IgSF is predominantly localized in the testes and brain. It belongs to the CAR subgroup of Ig cell adhesion proteins, which have been hypothesized to regulate connexin expression or localization. Here, we studied the putative link between mouse BT-IgSF and connexins in astrocytes, ependymal cells and neurons of the mouse. Global knockout of BT-IgSF caused an increase in the clustering of connexin43 (Gja1), but not of connexin30 (Gjb6), on astrocytes and ependymal cells. Additionally, we also found reduced expression levels of connexin43 protein in the cortex and hippocampus of knockout animals. Analysis of biocytin spread in hippocampal or cortical slices from mature mice of either sex revealed a decrease in astrocytic cell-cell coupling in the absence of BT-IgSF. The localization and expression of connexin36 (Gjd2) on neurons was not affected by the absence of BT-IgSF. Overall, our data indicate that the IgCAM BT-IgSF is essential for correct gap junction-mediated astrocyte-to-astrocyte and ependymal cell-to-ependymal cell communication. These data are discussed in the context of results obtained with knockouts of other members of the CAR protein subgroup.Summary statement In the brain astrocytes are organized in vast networks communicating through gap-junctions. Here, we demonstrate that the cell adhesion molecule BT-IgSF controls connexin43-mediated coupling in astrocytes and ependymal cells.Competing Interest StatementThe authors have declared no competing interest.