The propensity of proteins to stick together in large clumps — termed "protein aggregation "— is the culprit behind a variety of conditions including Huntington's, Alzheimer's and mad cow diseases. With this notoriety, protein aggregation is considered to be a bad accident of nature that happens when protein structure is mismanaged.
But new research published online in Developmental Cell, a journal of Elsevier's Cell Press, shows that, when kept in balance, protein aggregation has beneficial functions that allow cells to organize themselves in both time and space. The findings will be valuable as researchers design treatments for diseases that involve this process.
In the words of corresponding author Dr. Amy Gladfelter of the Dartmouth College Department of Biological Sciences in New Hampshire:
We discovered that protein aggregation is a way cells can create spatial patterns in molecules called transcripts, which are the intermediaries between the DNA and proteins. Positioning transcripts in specific places allows the cells to control where the encoded proteins are made and can influence the localization and function of proteins. This work redeems or elevates protein aggregation as not simply a terminal or negative function, but opens it up for examination as a mechanism exploited by cells for diverse purposes.Key to this process is a repetitive stretch of a protein building block called glutamine, which is known to serve as a glue for protein aggregates in disease. Through studies in yeast, Dr. Gladfelter and her team found that this repetitive stretch of glutamine is also used to cluster proteins for a normal cellular process, namely the regulation of a cell's division cycle. They note that many other proteins that are not associated with disease have similar glutamine stretches in their sequences.
"We hypothesize that many cell functions may be spatially organized by taking advantage of these repetitive glutamine tracts that are surprisingly common in many types of proteins," Dr. Gladfelter said.
As more examples of useful protein aggregation are identified, it should become clear how aggregates are regulated so that they do not reach toxic levels associated with diseases. "Understanding how this 'sweet spot' of aggregation is achieved will be useful for understanding pathways that are misregulated in established protein-aggregation disorders," Dr. Gladfelter explained. Also, as therapies are developed to treat protein-aggregation-based pathologies, it will be critical to consider that there may be many useful aggregates that should not be destroyed in the process of treating disease-causing aggregates.
Read the abstractProtein Aggregation Behavior Regulates Cyclin Transcript Localization and Cell-Cycle Control
[divider] [caption id="attachment_18867" align="alignleft" width="150"] Mary Beth O'Leary[/caption]
Reporting for Elsevier Connect
Mary Beth O’Leary is Press Officer and Associate Media Relations Manager for Cell Press (@CellPressNews), based in Cambridge, Massachusetts. She began her career at Cell Press as an Senior Editorial Assistant for the journal Cell before transitioning into a role as Marketing/Publicity Coordinator. In December, she moved into her position as Press Officer for Cell Press’s 29 journals. A graduate of the College of the Holy Cross in Worcester, Massachusetts, she studied literature and art history.