Cellular processes have been the subject of scientific queries for decades, with each new discovery opening up dozens more questions. Now, thanks to some curious UW-Madison researchers, the process a cell must go through to get rid of its trash is being dissected.
UW-Madison scientists are working to understand how proteins are degraded in a cell, a mechanism that is vital for normal cell functioning.
\[Protein degradation] is an essential process. The cell has to have this process, without it, [the cell] croaks,"" said Richard Vierstra, a UW-Madison molecular biologist leading the research.
Vierstra's research has focused on plants even though many are hoping the discoveries coming from this study will benefit humans as well as agricultural and recreational plants.
""This system is so conserved, [between plants and animals] that it is mechanically identical,"" Vierstra said.
As a result, learning how plant proteins find their cellular garbage is just as useful as discovering how the human system works. The hope is that knowing how unwanted plant proteins travel down the pathway of protein degradation will lead to new, deeper understandings of deadly human diseases.
""If [protein degradation] doesn't work well, then all kinds of diseases can occur' Parkinson, Alzheimer's and other neurological disorders,"" Vierstra said.
Plants make for easier subjects to test than their animal counterparts. One can circumnavigate the tense issues surrounding animal testing.
""Plants are good models. Testing and experimenting on them is easier,"" Vierstra said.
The research, funded by a four-year, $3.3 million grant by the National Science Foundation, will focus on modifying this pathway to benefit both medicine and agriculture.
By tinkering with the pathway, scientists might be able to make plants more resistant to viral infections, block inflammation from arthritis or prevent muscular problems in people who are bedridden.
But those research breakthroughs will not happen unless Vierstra and his team figure out how the degradation pathway chooses which proteins to destroy.
Each cell uses thousands of proteins to make its cell structure and basic cell machinery. But each day the cell also churns out another set of short-lived proteins that activate those cellular machines. These short-lived proteins need to be recycled through the protein degradation pathway.
Scientists once thought that cells timed the release of proteins, thereby regulating the protein degradation system. Now it appears that there is a much more complex system in place that is highly selective.
That system screens for proteins that were made improperly and for proteins only meant to exist for a short while. There are more than 1,000 short-lived proteins to remove.
This protein-breakdown system involves hundreds of different enzymes, which identify the proteins that need to be degraded. Once a protein is identified, an enzyme attaches a short protein ""tag"" to it, called ubiquitin.
That tag directs the cell to send that protein to structures that act like a cell's garbage dump, called lysosomes. Proteins inside the lysosomes are chopped into amino acids, the basic building blocks of life, which can then be reused to make other proteins.
Vierstra began investigating how cells destroy proteins after studying phytochrome, a protein that plants use to sense light.
Phytochrome disappears from plant cells after it is exposed to light. His lab was the first to show that ubiquitin, a protein that attaches to other proteins when their time is up, attaches to phytochrome, a short-lived protein, on its way through the protein-breakdown pathway.
Now Vierstra and his colleagues are working on identifying all of the enzymes and genes involved the degradation process. Using the small plant, Arabidopsis thaliana, a member of the mustard family, they are looking at which genes are involved in the process.
So far nearly 5 percent of the genes in Arabidopsis'around 1,250'are involved.
""We were completely surprised by the numbers. Our estimates were low. We were blown away [with the final number],"" Vierstra said.
Vierstra calls the protein degradation process part of the ""big three"" in cells'birth, death and taxes. Birth, he says, is the making of the proteins, death is the degradation of the proteins and taxes is the phosphorylization of proteins'a cellular system of accounting for and energizing protein structures.
""If you asked people a decade ago, they wouldn't have thought it would be that important. Now it's the big thing,"" Vierstra said.
