GlialCAM interactome identification: involvement in signaling and control of astrocyte self-organization

Dr. Raúl Estévez, group leader of the Institut of Neurosciences of the University of Barcelona and IDIBELL, ​​has led an investigation that has identified the GlialCAM protein interactome, whose gene causes the rare disease Megalencephalic Leukoencephalopathy with subcortical Cysts (MLC).

MLC is a rare type of leukodystrophy characterized by myelin edema. It is caused by autosomal recessive mutations in MLC1 or by autosomal recessive or dominant mutations in GLIALCAM, a gene discovered by the group led by Estévez. To advance the molecular functions of MLC1 and GLIALCAM, the GlialCAM interactome has been identified.

On the one hand, in collaboration with the group led by Cagla Eroglu, from Duke University, it has been shown that the lack of GlialCAM alters the location of Conexin 43, affecting the coupling through the gap junctions. This study has been published in the journal Neuron.

On the other hand, 2 orphan G-protein coupled receptors, GPR37L1 and GPRC5B, have been identified, which are involved in GlialCAM and MLC1-dependent intracellular signaling. These studies have suggested that MLC1 and GlialCAM function as a tetraspanin-like molecule coupled to an adhesion molecule. These studies have been published in the journal Human Molecular Genetics.

References

1.Baldwin, K., Tan, C., Strader, S., Jiang, C., Savage, J., & Elorza-Vidal, X. et al. (2021). HepaCAM controls astrocyte self-organization and coupling. Neuron. https://doi.org/10.1016/j.neuron.2021.05.025

2. Alonso-Gardón, M., Elorza-Vidal, X., Castellanos, A., La Sala, G., Armand-Ugon, M., & Gilbert, A. et al. (2021). Identification of the GlialCAM interactome: the G protein-coupled receptors GPRC5B and GPR37L1 modulate megalencephalic leukoencephalopathy proteins. Human Molecular Genetics. https://doi.org/10.1093/hmg/ddab155