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The IgCAM BT-IgSF (IgSF11) is essential for connexin43-mediated astrocyte-astrocyte and ependymal cell-cell coupling

Laura Pelz, Laura Dossou, Nine Kompier, René Jüttner, Gabrielle Siemonsmeier, Niklas Meyer, Elijah D. Lowenstein, Ines Lahmann, Helmut Kettenmann, Carmen Birchmeier, View ORCID ProfileFritz G. Rathjen
doi: https://doi.org/10.1101/2022.06.17.496568
Laura Pelz
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
2National Center for Tumor Diseases (NCT) Heidelberg and the German Cancer Research Center (DKFZ), Im Neuenheimer Feld 460, 69120 Heidelberg, Germany
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Laura Dossou
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
3Pfizer Pharma GmbH, Linkstraße 10, 10785 Berlin, Germany
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Nine Kompier
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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René Jüttner
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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Gabrielle Siemonsmeier
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
4McGill University, Integrated Program in Neuroscience, Irving Ludmer Building, 1033 Pine Avenue West, Montréal, Québec H3A 1A1, Canada
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Niklas Meyer
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
5Department of Microbiology, Oslo University Hospital, Sognsvannsveien 20, 02770 Oslo, Norway
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Elijah D. Lowenstein
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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Ines Lahmann
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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Helmut Kettenmann
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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Carmen Birchmeier
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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Fritz G. Rathjen
1Max-Delbrück-Center for Molecular Medicine, Robert-Rössle-Str. 10, DE-13092 Berlin, Germany
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  • ORCID record for Fritz G. Rathjen
  • For correspondence: rathjen@mdc-berlin.de
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Abstract

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 Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted June 17, 2022.
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The IgCAM BT-IgSF (IgSF11) is essential for connexin43-mediated astrocyte-astrocyte and ependymal cell-cell coupling
Laura Pelz, Laura Dossou, Nine Kompier, René Jüttner, Gabrielle Siemonsmeier, Niklas Meyer, Elijah D. Lowenstein, Ines Lahmann, Helmut Kettenmann, Carmen Birchmeier, Fritz G. Rathjen
bioRxiv 2022.06.17.496568; doi: https://doi.org/10.1101/2022.06.17.496568
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The IgCAM BT-IgSF (IgSF11) is essential for connexin43-mediated astrocyte-astrocyte and ependymal cell-cell coupling
Laura Pelz, Laura Dossou, Nine Kompier, René Jüttner, Gabrielle Siemonsmeier, Niklas Meyer, Elijah D. Lowenstein, Ines Lahmann, Helmut Kettenmann, Carmen Birchmeier, Fritz G. Rathjen
bioRxiv 2022.06.17.496568; doi: https://doi.org/10.1101/2022.06.17.496568

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