Gap junctions are collections of intercellular channels permeable to molecules less than 1 kDa, which play an important role in both electrical and chemical communication in cells of the central nervous system (CNS). The importance of gap junctions in the nervous system is underscored by the observation that connexin mutations are responsible for common heritable diseases affecting the CNS and peripheral nervous system (PNS). For example, mutations of connexin (Cx) 26 account for more than half of all cases of genetic deafness, affecting more than 1 in 2000 children. Mutations in Cx32 are responsible for the second most common inherited peripheral neuropathy, X-linked Charcot Marie Tooth disease (CMTX). CMTX affects the myelination of axons in the PNS, but surprisingly although oligodendrocytes abundantly express Cx32, there are no convincing reports that CNS myelin is affected in CMTX. It is believed that this may be due to functional gap junctions between oligodendrocytes and astrocytes. However, the connexins that are expressed in astrocytes and oligodendrocytes are not capable of forming functional channels. The purpose of this proposal is to further characterize Cx29, analyze functional coupling between oligodendrocytes and astrocytes, and determine what connexins are responsible for this coupling. I will perform dye transfer studies on spinal cord slices from adult mice to study glial coupling in the mature CNS. In addition, I will determine which connexins are expressed in oligodendrocytes and astrocytes. Once I have determined the protein localization of every known glial connexin, I will examine the channel properties of the identified connexins utilizing the paired Xenopus-oocyte system.
| Altevogt, Bruce M; Paul, David L (2004) Four classes of intercellular channels between glial cells in the CNS. J Neurosci 24:4313-23 |
| Altevogt, Bruce M; Kleopa, Kleopas A; Postma, Friso R et al. (2002) Connexin29 is uniquely distributed within myelinating glial cells of the central and peripheral nervous systems. J Neurosci 22:6458-70 |
