Let’s be honest…after a week of dissecting the article “Beyond cAMP: the regulation of Akt and GSK3 by dopamine receptors,” I barely understand any of it. At the beginning of the week, I was staring at the article hoping some information would penetrate into my brain but all I could conjure up was the question “What does that even mean?” As the week progressed, my senior level neurochemistry class and I have been trying to wrap our cumulative 2000+ IQ brains around this dense article. At the end of this long week, I realized that the more I understood about the article, the more questions kept coming up. Although I still do not fully understand the article, I will try to sum it up for you.
Honestly, I could probably go on and tell you about every little detail in this article but I do not think that anyone wants to read it. The main purpose of the article was to explore the Akt/GSK3 signaling cascade. This cascade it initiated when dopamine binds to its D2-receptors. When dopamine is bound, a complex is formed by β-arrestin, Akt, and PP2A. The PP2A protein in the complex dephosphorylates, removing a phosphate group, Akt, resulting in an inhibited Akt. The inhibited Akt cannot phosphorylate GSK3. Therefore, GSK3 is activated and allowed to cause other cellular responses. Did you understand any of that?
Here is a quick and dirty version: Dopamine–>form complex–>inactive Akt–>active GSK3–>cellular responses
If that does not help, here is a picture!
The article focuses on this signaling cascade because of its significance in the actions of antipsychotics, psychostimulants, and antidepressants. New information about the mechanisms of action is constantly being discovered by scientists. We have learned that some antipsychotic medications previously known as dopamine receptor blockers have been discovered to activate Akt which leads to inhibition of GSK3. Is that not exciting or what? Furthermore, lithium was once thought to modulate dopamine release and blocks its binding but lithium is now known to compete with magnesium and force the complex to fall apart. This allows PP2A to phosphorylate Akt. Thus, Akt can inhibit GSK3 via phosphorylation.
I am not even sure how I am containing my excitement right now. I may not understand every piece of information that this article is throwing at me but the fact that more and more new discoveries are being made has got me jacked. It is so interesting to me that we can get a medication like lithium to treat bipolar disorder but we had no idea on how it worked so well. I think that every person, scientist or not, should be jazzed at the fact that more and more information is being revealed about this mostly unknown pathway and its connections to the brain. I hope this helped anyone to understand what in the world the Akt/GSK3 signaling cascade is. In the words of Dr. Mach’s favorite movie character Ron Burgundy, “You stay classy, San Diego.”
Akt/GSK3 Pathway: Quick and Dirty Version
