Joint Appointments in:

• Occupational Therapy

Education/Training:

Teaching:

Human Gross Anatomy for Occupational Therapy and Physical Therapy Students (OT 322; PT 322). This course consists of lectures on the structure of the human body, with an emphasis on the musculoskeletal system, and of laboratory dissections corresponding to the lecture topics.

Fundamentals of Neuroscience for Occupational Therapy (OT 491). This new course offering is an introductory lecture and laboratory sequence covering the basics of human neural systems.

Human Gross Anatomy (for graduate students in the department).

Interests:

My interests in cell biology center on the question of how cells communicate. All cells are "wired" to receive and send signals, and all cells process those signals to bring about normal multicellular behavior. Most forms of cell-to-cell communication (also referred to as intercellular communication) require detection devices within the plasma membrane of a cell to recognize incoming signal molecules and generate secondary signal molecules inside the cell. This change in the signal molecule (called "signal transduction") is necessary because the first signal molecule cannot pass across the plasma membrane. In other cases, the signal molecule may cross the plasma membrane directly or via a transport system that carries the signal molecule into the cytoplasm. However, one form of cell-to-cell communication that occurs between adjacent cells actually bypasses the plasma membrane. It is this form of cell-to-cell communication (called gap junctional communication) that is studied in our laboratory.

In ways that are still not understood, sections of the plasma membrane of adjacent cells can come very close to each other and nearly touch &endash; separated by a gap of approximately 3 nanometers. Apparently, it is at these areas of close apposition that each of the cells provides channels that span the plasma membrane. Remarkably, these channels somehow dock together to form longer channels that cross both plasma membranes. As a consequence, each cell has direct access to the interior of the other via these channels, bypassing the plasma membrane. To distinguish between these two forms of channels, the smaller, precursor channel - in existence before docking has occurred - is called a "hemichannel" (or "connexon"). The larger channel formed by the docking of two hemichannels is simply called a gap junctional channel. Different forms of these channels are known to exist, but they all share certain characteristics, one of which is that the size of each channel is small enough to only allow small molecules (less than approximately 1000 molecular weight) to pass from one cell to the other. The regions of the cells that contains these channels form a junction between the two cells and is termed a "gap junction" because of the characteristic small space or gap bewteen the cells. Gap junctions typically have a large number channels aggregated together and many gap junctions typically are formed between cells. Gap junctions frequently are studied using the electron microscope. One method (freeze-fracture) allows visualization of individual channels. Another method of study is to inject a low molecular weight fluorescent tracer directly into one cell and observe the passage of the tracer from cell to cell using fluorescence microscopy. (The images on the home page and degree programs page show one such fluorescent tracer, called Lucifer yellow, after it had passed from the center, injected cell to all the cells in the field of view.)

Each hemichannel is composed of six identical protein subunits termed "connexins". The gap junctional channel, then, is formed by two connexin hexamers. The connexins are a family of proteins that share a basic topology and specific regions of conserved sequences. Nearly 20 different forms of connexin have been identified and a cell may contain more than one form.

A question currently under investigation in our laboratory concerns the mechanisms by which gap junctional communication is regulated. We are using various techniques in cell and molecular biology to study how gap junctional proteins (connexins) are "shipped" to the site of channel formation and how the assembly of gap junctional channels is controlled. Another area of investigation is whether and how gap junctions might support a calcium-based form of cell-to-cell communication manifest as intercellular calcium "waves".

Images From the Lab:

Figure 1. Connexin43 immunofluorescence showing the distribution of the protein in cultured cells. Bright fluorescence near cell-cell interfaces indicate the location of gap junctions

Figure 2. Fluorescence produced by a green fluorescent protein (GFP) fused to connexin43. Notice similarity with Fig. 1 in the pattern of distribution.

Figure 3. Same field of view as shown in Fig. 2, showing a phase contrast image overlayed with the Cx43/GFP fluorescence pseudo-colored green.

Selected Research Papers:

• Churchill, G. C., Atkinson, M. M., and Louis, C. F. (1996). Mechanical stimulation initiates cell-to-cell calcium signaling in ovine lens epithelial cells. J. Cell Science 109, 355-365.
  [click here for free full text Adobe Acrobat version]

• Atkinson, M. M., Lampe, P. D., Lin, H. H., Kollander, R., Li, X-R, and Kiang, D. T. (1995). Cyclic AMP modifies the cellular distribution of connexin43 and induces a persistent increase in the junctional permeability of mouse mammary tumor cells. J. Cell Science 108, 3079-3090.
  [click here for free full text Adobe Acrobat version]

• Miner, P., Lampe, P. D., Atkinson, M. M., and Johnson, R. G. (1995). Extracellular calcium and cadherins regulate the process of gap junction assembly between cells in culture. Prog. Cell Res. 4, 331-334.

• Liu, T-F., Li, H., Atkinson, M. M., and Johnson, R. G. (1995). Intracellular Lucifer yellow leakage from Novikoff cells in the presence of ATP or low extracellular Ca: Evidence for hemi-gap junction channels. Meth. Find. Exp. Clin. Pharmacol. 17, 23-28.

• Paulson, A. F., Johnson, R. G., and Atkinson, M. M. (1994). Intercellular communication is reduced by TPA and Ki-ras p21 in quiescent but not proliferating NRK cells. Exp. Cell Res. 213, 64-70.

• Crow, J. M., Atkinson, M. M., and Johnson, R. G. (1994). Micromolar levels of intracellular calcium reduce gap junctional permeability in lens cultures. Invest. Ophthalmol. Vis. Sci. 35, 3332-3341.

• Kiang, D. T., Kollander, R., Lin, H., LaVilla, S., and Atkinson, M. M. (1994). Measurement of gap junctional communication by fluorescence activated cell sorting. In Vitro Cell. Dev. Biol. 30A, 796-802.