In their May 2015 Scientific American article “Cellular Small Talk,” Dale W. Laird, Paul D. Lampe and Ross G. Johnson report on recent discoveries showing that the disruption of cellular structures called gap junctions can cause various diseases. Gap junctions consist of thousands of channels that allow ions (charged atoms) and small molecules to flow directly from the inside of one cell to that of a neighboring one. The article also delves into the discovery of gap junctions and tells the detective story of how investigators worked out the details of how cells make these massive structures.
Here, Lampe’s collaborator, Jason Iden of the University of Alberta, demonstrates how dye molecules can flow through gap junctions from one cell to another. Then, Jared Churko—a former student of Laird’s, now a postdoctoral fellow at Stanford University—maps out how gap junctions are formed.
Credit: Jason Iden, University of Alberta
To observe molecular exchange in action, Iden first loads a fluorescent dye into cells that are connected by gap junctions. He then uses a powerful laser to “bleach” the fluorescence from one of the connected cells. This cell still contains the dye but its fluorescence has been permanently quenched.
In the video the cell on the left is bleached at around the three-second mark. The dim cell “recovers” its fluorescence over time as dye molecules that are still shining brightly migrate through the gap junction channels from the cell on the right. In addition to the artificially introduced dye molecules, these cells are also exchanging a barrage of naturally occurring ions and small molecules, which they normally use to communicate.
Credit: Jared M. Churko, Stanford University
The animation shows the main events in gap junction assembly—from the synthesis of gap junction proteins, called connexins, to the opening of the channels, allowing ions and small molecules to pass. At the start of the animation, a ribosome (tan) is in the process of producing a connexin protein (aqua), based on information encoded in a messenger RNA molecule (purple). (This animation focuses on a connexin called Cx43, found in the heart, skin and other bodily sites.) As the connexin grows longer, an additional protein (blue) helps insert it into the membrane of the endoplasmic reticulum, the organelle in which this protein synthesis is taking place.
Once completed, connexins are then pinched off into vesicles (shown as a sphere) that carry them to the membrane of the nearby Golgi apparatus, where additional processing of membrane proteins occurs. There, six connexins come together to form a structure called a hemichannel (connexon), which is then carried by another vesicle to the cell’s outer (plasma) membrane. At this stage, the hemichannels can open and allow the cell to exchange different ions and small molecules (shown as colored balls) with the external environment.
When one hemichannel encounters another in the membrane of a neighboring cell, the two can dock with one another, forming a channel that connects the interior of one cell to the interior of its neighbor; a collection of these docked channels constitutes a gap junction. The subsequent exchange of ions and molecules through the channels represents an important form of intercellular communication.