If I’ve learned anything while at Concordia, it’s that there’s always something else I can learn. This week in neurochemistry only helped to make this more evident. After the first read-through of the article “Beyond cAMP: the regulation of Akt and GSK3 by dopamine receptors,” it really felt like I haven’t learned anything. However, after hashing it all out in class, we were able to piece together a very promising and intriguing protein signaling cascade. So why should we care about this pathway? Whether we realize it or not, every process that occurs in our body is ultimately the result of chemical reactions. When these reactions start to go wrong and processes start to fail we wind up in a pathological state.
So how does this all relate to Akt, GSK3, and dopamine? Dopamine is a chemical that acts within the brain and the rest of the body. Referred to as a neurotransmitter, dopamine is used to send signals between neurons. Dopamine is able to signal the occurrence of events in the body by binding to one of five dopamine receptors. When dopamine binds to the D2 receptor a signaling event involving Akt and GSK3 is initiated. Here’s how it works: dopamine binds the D2 receptor, a complex of β-arrestin, Akt and PP2A is formed, PP2A takes a phosphate group off of Akt (causing its inhibition), and GSK3 is activated. If you’re confused, that’s okay. Basically all you need to remember is that the binding of dopamine to D2 receptors causes the activation of GSK3.
Right about now, you’re probably thinking “Cool, and I care why?” Researchers have been studying this pathway, specifically GSK3 and the molecules it acts on after it is activated. It is now believed that a variety of disorders are associated with the Akt/GSK3 pathway. These conditions include: depression, schizophrenia, bipolar disorder, Parkinson’s Disease, and addiction. In addition, various cell processes are now believed to be implicated with this pathway. Studying pathways such as the Akt/GSK3 pathway offers a way to learn more about these conditions. In addition, a better understanding of the mechanism by which these pathologies present could bring to light novel treatments.
This pathway exemplifies the idea that there is always something else to learn. Although researchers have been studying these conditions for some time, they are just now beginning to discover a mechanism by which they MIGHT work. From a scientist’s perspective, the most exciting thing about this is not what they’ve already discovered about the Akt/GSK3, but the fact that it is just scratching the surface. There is undoubtedly a variety of targets that are downstream from the GSK3 protein that are involved in countless mechanisms. Even more, this is just one pathway; the body is filled with signaling pathways that make you function! While the discovery of the Akt/GSK3 pathway and its targets is exciting, it’s even more exciting to think of where it may take us.
Akt/GSK3 Protein signaling: The Other White Meat
