Serotonin, the neurotransmitter that is believed to play a part in regulating mood as well as appetite and sleep, is now being tracked in the body for the first time. Researchers at Vanderbilt University in Nashville have completed a decade-long quest to attach tiny fluorescent beads to a "transporter" protein that regulates serotonin. The study was reported in the June 27th issue of the Journal of Neuroscience.
According to a press release from the university, the protein extends through the membrane that forms the nerve’s outer surface and acts like a nano-sized vacuum cleaner to suck serotonin molecules into the cell body and away from serotonin target receptors on other cells. In this way, the protein helps regulate the concentration of serotonin in the area around the cell. Serotonin transporters are an important research subject because they are the target for the most common drugs used to treat depression, including Prozac, Paxil, and Lexapro.
The release quotes chemistry graduate student Jerry Chang, who developed the tagging technique, as saying, “In the past, we have been limited to snapshots that show the location of transporter molecules at a specific time. Now we can follow their motion on the surface of cells in real time and see how their movements relate to serotonin uptake activity.”
The fluorescent tags allowed the scientists to see that there are two distinct populations of transporter, those that can travel freely around the membrane and those that act as if they are unable to move. The research team found that the immobile transporters were located in "rafts." When the researchers stimulated the cell to increase transporter activity, they were surprised at what happened. “We found that the transporters in the rafts began to move much faster whereas the motion of the other population didn’t change at all,” said Sandra Rosenthal, one of the directors of the study. Since the mobilized transporters do not leave the rafts, they appear to whizz around inside a confined compartment, as if released from chains that normally keep them subdued. The university release says that these observations suggest it is likely that the two populations are controlled by different regulatory pathways, those tethered to rafts and those that move freely around the membrane.
“Now that we can watch transporter regulation actually happening, we should be able to figure out the identity of the anchoring proteins and the signals these proteins respond to that permit transporters to switch back and forth between low and high activity levels,” said Randy Blakely, the Allan D. Bass Professor of Pharmacology and Psychiatry. “Currently, antidepressant drugs must fully shut down the brain’s serotonin transporters to achieve a clinical benefit. By understanding the basic mechanisms that naturally turn serotonin transporter activity up and down, maybe we can develop medications that produce milder side-effects and have even greater efficacy."