A dysfunction in the chloride channel in astrocytes, involved in megalencephalic leukoencephalotaphy

A research study led by researchers of the University of Barcelona and published in the journal Human Molecular Genetics, has provided a better understanding of a physiopathological process in astrocytes involved in megalencephalic leukoencephatolaphy (MLC), rare type of leukodistrophy. The study has been co-led by the researchers of the UB Xavier Gasull, from the Institute of Neurosciences of the UB and IDIBAPS, and Raúl Estévez, IDIBELL-UB researcher, both members of the Rare Diseases Networking Biomedical Research Centre (CIBERER).

The study reaches the conclusion that ClC-2 (chloride channel), GlialCAM and MLC proteins (the latter ones are altered in MLC) are linked forming a ternary complex when astrocytes are depolarized, like in situations of high neural activity. The association of ClC-2 with GlialCAM and MLC1 changes the ClC-2 activation, which leads it to be open to positive potentials, and to take part in compensation of positive charges in glial cells adding chloride. Researchers point that a defect in this compensation may contribute to the pathogenesis of the MLC disease.

Apart from making a hypothesis on the possible biochemical function of GlialCAM and MLC1 proteins, this study gives a physiological function to the ClC-2 and allows the researchers to describe an altered physiopathological process in the MLC, which is necessary to design future therapeutic interventions.

Article reference:

Sònia Sirisi, Xabier Elorza-Vidal, Tanit Arnedo, Mercedes Armand-Ugón, Gerard Callejo, Xavier Capdevila-Nortes, Tania López-Hernández, Uwe Schulte, Alejandro Barrallo-Gimeno, Virginia Nunes, Xavier Gasull, Raúl Estévez. Depolarization causes the formation of a ternary complex between GlialCAM, MLC1 and ClC-2 in astrocytes: implications in megalencephalic leukoencephalopathy. Human Molecular Genetics doi: 10.1093/hmg/ddx134

Image: Translocation of ClC-2 in astrocytes under depolarizing conditions