The Distribution and Functional Properties of PMLD-Linked CX47 Mutations on CX47/CX47 Homotypic and CX47/CX43 Heterotypic Gap Junctions
نویسندگان
چکیده
Gap junctions (GJ) allow direct intercellular communication, and consist of connexins (Cx). In the mammalian central nervous system, oligodendrocytes express Cx29, Cx32 and Cx47, whereas astrocytes express Cx26, Cx30 and Cx43. Cx47/Cx47 GJs couple oligodendrocytes, and Cx47/Cx43 channels are the primary heterotypic GJs at oligodendrocyte/astrocyte junctions. Interestingly, mutations in Cx47 have been linked to central hypomyelinating Pelizaeus Merzbacher-like Disease (PMLD). My aim is to determine the cellular distribution and functional properties of PMLD-associated Cx47 mutants (I46M, G149S, G236R, G236S, M286T, T398I). All mutants were detected at the cell-cell interface. These mutants, except G149S and T398I, showed no electrical coupling in both Cx47/Cx47 and Cx47/Cx43 GJ channels. G149S and T398I formed homotypic and heterotypic channels of apparently normal functions. These results suggest that the tested Cx47 mutants, except G149S and T398I, lead to PMLD likely due to disruption in Cx47/Cx47 and/or Cx47/Cx43 GJ functions in the macroglial network. Dedication I would like to dedicate my thesis to my beloved mom and dad. v Acknowledgments I would like to thank, first and foremost, my supervisor Dr. Donglin Bai for the opportunity to expand my knowledge in science. His assistance and guidance along with his vast knowledge of electrophysiology and encouragement allowed me to gain invaluable experience in scientific research. I am also grateful to all my committee members, Drs. for all the precious advice and support. I would like to express my appreciation towards the Bai laboratory, especially Drs. Xiang-Qun Gong and Yiguo Sun and Li Xin for all the help and advice for laboratory techniques and technical support. I could not have finished my project without your hands-on advice. It has been a great pleasure to work with you all. Lastly, I thank all my family and friends for unconditional support and patience. Thank you for being so understanding and supportive, and for never ending motivations.
منابع مشابه
Two distinct heterotypic channels mediate gap junction coupling between astrocyte and oligodendrocyte connexins.
Genetic diseases demonstrate that the normal function of CNS myelin depends on connexin32 (Cx32) and Cx47, gap junction (GJ) proteins expressed by oligodendrocytes. GJs couple oligodendrocytes and astrocytes (O/A channels) as well as astrocytes themselves (A/A channels). Because astrocytes express different connexins (Cx30 and Cx43), O/A channels must be heterotypic, whereas A/A channels may be...
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