Abstract

The purpose of the proposed research project will be to study the molecular basis for cell-cell communication via gap junctions, and to study the biological role of gap junctional communication during embryonic development and tissue differentiation. The present proposal contains an integrated effort utilizing protein chemical, ultrastructural, immunological, biophysical, and recombinant DNA approaches.
The specific aims i nclude studies on: characterization of isolated gap junctions; generation of gap junction antibodies; reconstitution of gap junction channels; synthesis and biogenesis of gap junctions in vitro and in vivo; biological role of communication in embryonic development; and relationship between communication and gene expression during cell differentiation. We will continue the initial observations on fibrinogen that have resulted from our current studies on gap junctions. Thus far, these studies have provided the basis for identifying fibrinogen as a major component of the extracellular matrix (ECM) of a variety of tissues.
The specific aims i nclude studying: the characteristics of ECM fibrinogen; figrinogen gene expression in various tissues; biosynthesis of ECM fibrinogen in vitro and in vivo; developmental expression of fibrinogen in embryos; and the biological role of fibrinogen during embryonic development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM037904-04
Application #
3293711
Study Section
Cellular Biology and Physiology Subcommittee 1 (CBY)
Project Start
1986-07-01
Project End
1990-11-30
Budget Start
1989-07-01
Budget End
1990-11-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost

  Institution

Name
Scripps Research Institute
Department
Type
DUNS #
City
La Jolla
State
CA
Country
United States
Zip Code
92037

  Publications

Lagree, Valerie; Brunschwig, Karin; Lopez, Patricia et al. (2003) Specific amino-acid residues in the N-terminus and TM3 implicated in channel function and oligomerization compatibility of connexin43. J Cell Sci 116:3189-201
Baruch, A; Greenbaum, D; Levy, E T et al. (2001) Defining a link between gap junction communication, proteolysis, and cataract formation. J Biol Chem 276:28999-9006
Baldo, G J; Gong, X; Martinez-Wittinghan, F J et al. (2001) Gap junctional coupling in lenses from alpha(8) connexin knockout mice. J Gen Physiol 118:447-56
Unger, V M; Kumar, N M; Gilula, N B et al. (1999) Expression, two-dimensional crystallization, and electron cryo-crystallography of recombinant gap junction membrane channels. J Struct Biol 128:98-105
Risek, B; Pozzi, A; Gilula, N B (1998) Modulation of gap junction expression during transient hyperplasia of rat epidermis. J Cell Sci 111 ( Pt 10):1395-404
Gong, X; Baldo, G J; Kumar, N M et al. (1998) Gap junctional coupling in lenses lacking alpha3 connexin. Proc Natl Acad Sci U S A 95:15303-8
Falk, M M; Gilula, N B (1998) Connexin membrane protein biosynthesis is influenced by polypeptide positioning within the translocon and signal peptidase access. J Biol Chem 273:7856-64
Falk, M M; Buehler, L K; Kumar, N M et al. (1997) Cell-free synthesis and assembly of connexins into functional gap junction membrane channels. EMBO J 16:2703-16
Risek, B; Gilula, N B (1996) Gap junction regulation during preterm labor in the rat: multiple effects of the antiprogesterone RU486. Biol Reprod 55:525-35
Buehler, L K; Stauffer, K A; Gilula, N B et al. (1995) Single channel behavior of recombinant beta 2 gap junction connexons reconstituted into planar lipid bilayers. Biophys J 68:1767-75

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