The distribution and functional properties of Pelizaeus Merzbacher-like disease-linked Cx47 mutations on Cx47/Cx47 homotypic and Cx47/Cx43 heterotypic gap junctions

Gap junctions (GJs) allow direct intercellular communication, and consist of connexins (Cxs). In the mammalian central nervous system, oligodendrocytes express Cx47, Cx32 and Cx29, whereas astrocytes express Cx43, Cx30 and Cx26. Homotypic Cx47/Cx47 GJs couple oligodendrocytes, and heterotypic Cx47/Cx43 channels are the primary GJs at oligodendrocyte/astrocyte junctions. Interestingly, autosomal recessive mutations in the gene GJC2 encoding Cx47 have been linked to a central hypomyelinating disease termed, Pelizaeus Merzbacher-like disease (PMLD). Our aim is to determine the cellular distribution and functional properties of PMLD-associated Cx47 mutants (I46M, G149S, G236R, G236S, M286T and T398I). Expressing GFP-tagged mutant versions of Cx47 in gap junction deficient model cells revealed that these mutants were detected at the cell-cell interface similar to that observed for wild type Cx47. Furthermore, four of the six mutants showed no electrical coupling in both Cx47/Cx47 and Cx47/Cx43 GJ channels. These results suggest that most of PMLD-linked Cx47 mutants disrupting Cx47/Cx47 and Cx47/Cx43 GJ function in the glial network, which may play a role in leading to PMLD symptoms.

Source: BJ Cell - April 2, 2013 Category: Biochemistry Authors: M Kim, G B Gloor, D Bai Tags: BJ Disease Source Type: research