What about trafficking?

One other word that has frequently been mentioned in my blogs is 'trafficking'. Many people, even biologists might not understand what trafficking is or how it works. Thus, I think I will write another blog giving people some background of my research, in this case, trafficking.

Often, people would consider a negative connotation associated to the word 'trafficking'. For example, human trafficking, or drug trafficking. However in the scientific world, trafficking is not nearly as bad as its normal meaning. In fact, protein trafficking might have been an important feature that allows the development, and the evolution from prokaryotic to eukaryotic cells. There have been speculations that the protein trafficking systems would have to be evolved prior to the eukaryotic cells. Because simple cellular diffusion is often not sufficient as a method of substance transportation within eukaryotic cells, thus substance movements had to be archived via a specialized transport mechanism in eukaryotic cells rather than just diffusion.

Protein trafficking, or translocation involves rapid intracellular shuttlings of molecules packed in transportive vesicles. Cellular trafficking is often accomplished by following cellular tracks composed of cytoskeletonal proteins using motor proteins. In detail, some protein appeared to use different types of cytoskeleton tracks depending on the phase of the cell cycle. Translocation allows cells to store away unused proteins in vesicles, while rapidly mobilize and deploy them when a demand emerges. Though translocation, a cell greatly reduces its protein turn-over rates, which in turn, reduces the energy expenditure of a cell while performs all of its function at a timely fashion. It has been reported that the effects of translocation can be often seen within half an hour or less.

One of the important organelle used during trafficking is the Golgi apparatus. It plays two central roles in many cellular trafficking events; it is involved in protein synthesis and delivery, as well as internalizing molecular processes via endocytic. In more detail, brefeldin A, a chemical inhibits protein synthesis by blocking membrane trafficking from the endoplasmic reticulum to the Golgi apparatus proves that protein translocation is a necessary step in protein synthesis, as protein synthesis is often requires different organelles. In another study, it has also been found that besides protein synthesis, progression of murine oocyte maturation possibly also requires functional membrane trafficking.

Trafficking is a common phenomenon that has been observed across many species. For example, in humans, copper pumps are trafficked to the cell membrane from the E.R. in the presence of excessive cellular copper ions. Recently, trafficking has also been shown to be regulated by environmental cues. For example, in electric fishes, voltage-gated sodium channels are circadianly trafficked into the excitable membranes of electrogenic cells before conducting weak electric field for communication and navigation.

In conclusion, protein trafficking is not only a process that can greatly reduce the energy expenditure of a cell, while allowing all the cellular processes to run smoothly; it is also crucial in protein synthesis. Translocation might even be one of the features that allowed the evolution of higher organisms!

So, what exactly is a Na+/K+-ATPase

With all that many blogs thus far dedicated to this ATPase, I just realized maybe not everyone knows what a Na+/K+-ATPase is or what it does. Well, for those who are not as familiar with the Na+/K+-ATPase, here is a short background for ya.

The Na+/K+-ATPase, is a small, but nonetheless important membrane-bound active ion-transporter protein that is expressed in all multicellular organisms. This ATPase belongs the P-type ion-motive APTase family, in which also contains other H+, H+/K+, Ca2+, and heavy metal pumps. The Na+/K+-ATPase is a heterodimer containing alpha- and beta-subunits. The alpha-subunit is the catalytic subunit with a size of approximately 100kDa. In mammals, it has been noted the ATPase is composed of at least three a-subunits and three b-subunits. However, there is no evidence indicating the expression of different isoforms in insects, which is the one I'm studying. The active transport of ions across membranes by this ATPase is the greatest single energy-consuming process in most cells. Depending on the tissue type, the Na+/K+-ATPases consume between 5 – 40% of the cellular energy expenditure. Thus despite its small size, the Na+/K+-ATPase is a very important protein, especially in sensor/nervous/muscular cells where it is essential in conducting action potentials, and in renal cells where it regulates the reaborption of sodium.

 The key roles of this ATPase include, but not limited to regulating cell volume regulation, providing ion gradients that facilitate the movement of other solutes, and acting as a physiological regulator. Moreover, researchers have also demonstrated that in cardiac muscles, the Na+/K+-ATPase can even act as an indirect regulator of the myocardium contraction. In addition, the ion gradients provided by the ATPase across plasmalemmal membranes are also critical to cells, especially to those sensory, muscular and nervous cells.

Balanced Na+ and K+ ion-gradients across the neuronal membranes are essential for neurons to generate and conduct action potentials along their axons. The Na+/K+-ATPase assists neurons to sustain their Na+ and K+ homeostasis by shuffling Na+ and K+ ions across the plasma membranes. Through per ATP expenditure, this ion-transporter protein exports 3 Na+ ions out to the extracellular space for every 2 K+ ions imported into the cytoplasm. Due to the vital role of the Na+/K+-ATPase in sustaining action potentials, which is depended on the establishment of the Na+ and K+ homeostasis across the cellular membranes, the activity of this ATPase is targeted by multiple regulatory mechanisms to ensure its correct functioning. Failure in the regulatory mechanisms would often lead to deleterious effects.

 

To ensure its survival, a cell has overlapping mechanisms to failproof its regulations on the Na+/K+-ATPase. For example, the ATPase activity is enhanced by its substrates, or inhibited by cardiac glycosides. In addition, the Na+/K+-ATPase enzyme and substrate affinity also varies according to the cellular environment. Researchers have demonstrated that the addition of cytoskeletal proteins can increase the affinity of Na+/K+-ATPase for ATP. Furthermore, various hormones, such as insulin, and other signalling molecules can affect the activity of the protein positively or negatively. Moreover, the activity of the ATPase is also subject to regulation by reversible protein phosphorylation.

As you can sell, despite the relatively small size of the Na+/K+-ATPase, the rigorousity of the mechanisms that are regulating the Na+/K+-ATPase is undeniable. These mechanisms proved the importance of this protein and ensured that it is always being kept under its optimal condition to maintain the Na+ and K+ ion-gradients, a duty that is critical to an organism’s survival.