Date of Award
Master of Science
Physiology and Pharmacology
Dr. Donglin Bai
Gap junction (GJ) channels, a conduit for intercellular communication between adjacent cells, are composed of connexins (Cxs). Human macroglial cells express non-overlapping Cxs with oligodendrocytes expressing Cx47, Cx32 and Cx29 while astrocytes express Cx43, Cx30 and Cx26. Intercellular communication between oligodendrocytes and astrocytes depends on heterotypic GJ channels, predominantly Cx47/Cx43 heterotypic channels. Mutations in either Cx47 or Cx43 have been linked to central hypomyelination diseases, suggesting a critical role of Cx47/Cx43 GJ channels. Moreover, patients with Cx43 mutations exhibit pleiotropic phenotypes with only some mutations linking to central hypomyelination. Our aim is to study functional changes of hypomyelination-linked Cx43 mutants K134N, G138R, and V96A against non- hypomyelination-linked Cx43 mutants R76H, H194P, and V96M. We found that all mutants were functionally impaired in either homotypic or heterotypic GJ channel formation with Cx47, suggesting that electrical coupling via the heterotypic Cx43/Cx47 GJ channels may not be critical in the maintenance of central myelination.
MacDonald, Andrew, "THE CONSEQUENCE OF ODDD HYPOMYELINATION-LINKED Cx43 MUTATIONS ON HETEROTYPIC GAP JUNCTIONAL INTERCELLULAR COMMUNICATION BETWEEN Cx43/Cx47 GAP JUNCTION CHANNELS" (2011). Digitized Theses. 3526.