Abstract

Previously, we showed that mutations in connexin32 (Cx32) cause a form of Charcot-Marie-Tooth disease, a demyelinating neuropathy of the peripheral nervous system (PNS). In addition, we showed in mouse knockout studies Cx32 and Cx47 provide redundant functions necessary for normal myelination in the central nervous system (CNS), an observation confirmed by the recent discovery that Cx47 mutations cause Pelizaeus-Merzbacher-Like disease (PMLD), characterized by abnormalities in CNS myelin. Thus, maintenance of myelin in both CNS and PNS requires connexin expression. However, it is not at all clear how oligodendrocytes and Schwann cells use connexins and why they are critical for normal myelination. We propose to define the separate and interacting roles of connexins in myelination and why mutations cause disease using a combination of targeted gene ablation and functional analysis of connexin channel activity. '.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037751-24
Application #
7884228
Study Section
Intercellular Interactions (ICI)
Program Officer
Rivera-Rentas, Alberto L
Project Start
1986-12-01
Project End
2012-06-30
Budget Start
2010-07-01
Budget End
2012-06-30
Support Year
24
Fiscal Year
2010
Total Cost
$419,513
Indirect Cost

  Institution

Name
Harvard University
Department
Biology
Type
Schools of Medicine
DUNS #
047006379
City
Boston
State
MA
Country
United States
Zip Code
02115

  Publications

Hou, Mingli; Li, Yaqiao; Paul, David L (2013) A novel, highly sensitive method for assessing gap junctional coupling. J Neurosci Methods 220:18-23
Beaumont, Michael; Maccaferri, Gianmaria (2011) Is connexin36 critical for GABAergic hypersynchronization in the hippocampus? J Physiol 589:1663-80
Postma, Friso; Liu, Cheng-Hang; Dietsche, Caitlin et al. (2011) Electrical synapses formed by connexin36 regulate inhibition- and experience-dependent plasticity. Proc Natl Acad Sci U S A 108:13770-5
Brown, Timothy M; Allen, Annette E; Wynne, Jonathan et al. (2011) Visual responses in the lateral geniculate evoked by Cx36-independent rod pathways. Vision Res 51:280-7
Chai, Zhifang; Goodenough, Daniel A; Paul, David L (2011) Cx50 requires an intact PDZ-binding motif and ZO-1 for the formation of functional intercellular channels. Mol Biol Cell 22:4503-12
Magnotti, Laura M; Goodenough, Daniel A; Paul, David L (2011) Deletion of oligodendrocyte Cx32 and astrocyte Cx43 causes white matter vacuolation, astrocyte loss and early mortality. Glia 59:1064-74
Magnotti, Laura M; Goodenough, Daniel A; Paul, David L (2011) Functional heterotypic interactions between astrocyte and oligodendrocyte connexins. Glia 59:26-34
Pan, Feng; Paul, David L; Bloomfield, Stewart A et al. (2010) Connexin36 is required for gap junctional coupling of most ganglion cell subtypes in the mouse retina. J Comp Neurol 518:911-27
Imbeault, Sophie; Gauvin, Lianne G; Toeg, Hadi D et al. (2009) The extracellular matrix controls gap junction protein expression and function in postnatal hippocampal neural progenitor cells. BMC Neurosci 10:13
Hou, Jianghui; Renigunta, Aparna; Gomes, Antonio S et al. (2009) Claudin-16 and claudin-19 interaction is required for their assembly into tight junctions and for renal reabsorption of magnesium. Proc Natl Acad Sci U S A 106:15350-5

Showing the most recent 10 out of 79 publications