Abstract

The proposed research will study the structure and function of the gap junction as the site of intercellular communication. The junction structure will be studied using techniques of x-ray diffraction, electron microscopy, and biochemistry. Gap junctions from heart, liver and lens tissue will be compared. Comparison will be made by peptide mapping of proteolysis fragments of principal polypeptides electrophoretically isolated from different gap junction preparations. The function and biogenesis of gap junctions will be studied by raising monoclonal antibodies to the lens gap junction principal peptide. The antibodies will be used to study the cell and molecular biology of gap junction biosynthesis and assembly, looking for primary transcripts of mRNA from lens homogenates, and extrajunctional antigens with fluorescent antibodies. Freeze substitution autoradiography will be used to study metabolic cooperation at the organ level.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM018974-14
Application #
3269466
Study Section
Molecular Cytology Study Section (CTY)
Project Start
1975-01-01
Project End
1987-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
14
Fiscal Year
1985
Total Cost
Indirect Cost

  Institution

Name
Harvard University
Department
Type
Schools of Medicine
DUNS #
082359691
City
Boston
State
MA
Country
United States
Zip Code

  Publications

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
Altevogt, Bruce M; Paul, David L (2004) Four classes of intercellular channels between glial cells in the CNS. J Neurosci 24:4313-23
Menichella, Daniela M; Goodenough, Daniel A; Sirkowski, Erich et al. (2003) Connexins are critical for normal myelination in the CNS. J Neurosci 23:5963-73
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
Bruzzone, R; White, T W; Paul, D L (1994) Expression of chimeric connexins reveals new properties of the formation and gating behavior of gap junction channels. J Cell Sci 107 ( Pt 4):955-67
Bruzzone, R; White, T W; Scherer, S S et al. (1994) Null mutations of connexin32 in patients with X-linked Charcot-Marie-Tooth disease. Neuron 13:1253-60
Bruzzone, R; Haefliger, J A; Gimlich, R L et al. (1993) Connexin40, a component of gap junctions in vascular endothelium, is restricted in its ability to interact with other connexins. Mol Biol Cell 4:7-20
Flint, K K; Rosbash, M; Hall, J C (1993) Transfer of dye among salivary gland cells is not affected by genetic variations of the period clock gene in Drosophila melanogaster. J Membr Biol 136:333-42
Musil, L S; Goodenough, D A (1993) Multisubunit assembly of an integral plasma membrane channel protein, gap junction connexin43, occurs after exit from the ER. Cell 74:1065-77

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