Cellular basis of ClC-2 Cl- channel-related brain and testis pathologies [Membrane Biology]

Alexandros G.Sfakianakis shared this article with you from Inoreader Cellular basis of ClC-2 Cl- channel-related brain and testis pathologies [Membrane Biology] Μέσω JBC Papers in Press The ClC-2 chloride channel is expressed in the plasma membrane of almost all mammalian cells. Mutations that cause the loss of ClC-2 function lead to retinal and testicular degeneration and leukodystrophy, whereas gain of function mutations cause hyper­aldosteronism. Leukodystrophy is also observed with a loss of GlialCAM, a cell adhesion molecule which binds to ClC-2 in glia. GlialCAM changes the localiz ation of ClC-2 and opens the channel by altering its gating. We now used cell-type specific deletion of ClC-2 in mice to show that retinal and testicular degeneration depend on a loss of ClC-2 in retinal pigment epithelial cells and Sertoli cells, respectively, whereas leukodystrophy was fully developed only when ClC-2 was disrupted in both astrocytes and oligodendrocytes. The leukodystrophy of Glialcam-/- mice could not be rescued by crosses with Clcn2op/op mice in which a mutation mimics the 'opening' of ClC-2 by GlialCAM. These data indicate that GlialCAM-induced changes in biophysical properties of ClC-2 are irrelevant for GLIALCAM-related leukodystrophy. Taken together, our findings suggest that the pathology caused by Clcn2 disruption results from disturbed extracellular ion homeostasis and identifies the cells involved in this process. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.