Johnson's Lab interests focus on the role of gap junctions in intercellular communication. Within these junctions, membrane channels at the surface of one cell are linked to similar channels in the membranes of opposed cells, providing a pathway for the exchange of small molecules between cells. These interactions are thought to be critical for the control of cell growth, for normal embryonic development and for a variety of other processes. The biomedical importance of gap junctions is underscored by recent work on gene "knock-outs" in mice and on human mutations involving gap junction proteins. These mutations are responsible for a number of genetic diseases.
Studies in the laboratory address the regulation of junctional communication, both via mechanisms related to the assembly of gap junctions and to the "gating" of junctional channels in mature junctions. Questions relate to the molecular components of the developing junctions (e.g., members of the connexin gene family), the requirements of assembly and the various controls over the process, including membrane trafficking, connexin phosphorylation and signaling at the cell surface. To illustrate, agents which stimulate connexin phosphorylation, e.g., tumor promoters, dramatically modify both the assembly of junctions and the open state of junctional channels. In addition, agents which elevate cAMP in cells are able to enhance gap junction assembly, apparently through an effect on the trafficking of gap junction precursors from inside to the plasma membrane (along microtubules). The experimental work on this project is carried out using cultured cells.
Two other projects involve work of a developmental nature. The first addresses the role of gap junction communication in the zebrafish embryo, specifically in the notochord, which is a source of important signals in the early embryo. The notochord influences the development of the neural tube and somites, along with other cells. The second developmental project examines the role of gap junctions in synchronizing the beating of neighboring heart cells, as in adult heart.
Selected Publications (Pubmed Search)
Chatterjee, Valdimarsson, Finis, Krufka, Kozlowski, Johnson, and Lo. (2005). Structure, function and expression of the zebrafish connexin43 gene. Devel. Dynamics. 233:890-906
Hur, KC, J. Shim and RG Johnson (2003). A potential roll for Cx43-hemichannels in staurosporin-induced apoptosis. Cell Communications and Adhesion 10:271-277.
Johnson, R.G., H.Y. Li, T. Myslajek, T.F. Liu, C. Elfgang, K. Willecke, M. Atkinson, D. Laird, and J.D. Sheridan, (2003) Gap junction hemichannels: Dye uptake is inhibited by connexin antibodies, stimulated mechanically and detected with nine different connexins.
Johnson, R.G., R.A. Meyer, X.-R. Li, D. Preus, L. Tan, H.Y. Li, A.F. Paulson, D.W. Laird and J. Sheridan (2002) Gap junctions assemble in the presence of cytoskeletal inhibitors, but enhanced assembly requires microtubules. Exper. Cell Res. 275:67-80.
Lampe, P.D., Q. Qui, R.A. Meyer, E.M. TenBroek, T.F. Walseth, T.A. Starich, H.Y. Li, and R.G. Johnson (2001) Gap junction assembly: Pertussis toxin-sensitive G proteins regulate the distribution of connexin43 within cells. Amer. J. of Physiol. 281:C1211-22.
TenBroek, E., P.D. Lampe, Reynhout, J., T. Christen and R.G. Johnson. (2001) The C-terminus of connexin43 is required for the up-regulation of gap junction assembly by cAMP. J. of Cell Biol. 155:1307-1318.
Lampe, P.D., E.M. TenBroek, J.M. Burt, W.E. Kurata, R.G. Johnson, A.F. Lau (2000) Phosphorylation of connexin43 on serine 368 by protein kinase C regulates gap junctional communication. J. Cell Biol. 149:1503-12.
A.F. Paulson, P. Lampe, R.A. Meyer, E.M. TenBroek, M.M. Atkinson, T. Walseth, P. and R.G. Johnson (2000) Cyclic AMP and LDL trigger gap junction assembly through a stimulation of connexin trafficking. J. Cell Sci. 113:3037-49.
Essner, J.J., R.G. Johnson, P.B. Hackett (1999) Overexpression of thyroid hormone receptor a1 during zebrafish embryogenesis disrupts hindbrain patterning and implicates retinoic acid receptors in the control of hox gene expression. Differentiation, 65:1-11.
Krufka, A., R.G. Johnson, C.C. Wylie, and J. Heasman (1998). Evidence that dorsal-ventral differences in gap junctional communication in early Xenopus embryos are generated by b-catenin independent of all adhesion effects. Developmental Biology 200:92-102.