By Emily Hawes
SNARE proteins determine how tiny membrane pouches called vesicles fuse with different cellular compartments to transport cargo and organize cells. How cells correctly target individual SNAREs to their destination is poorly understood, but new Vanderbilt research is shedding light on the process. The findings could have important implications for the study of neurodegenerative diseases, some of which are associated with dysfunction in vesicle fusion.
The laboratories of Todd Graham, Stevenson Professor of Biological Sciences at the College of Arts and Science, Jason MacGurn, associate professor of cell and developmental biology, and Lauren Jackson, associate professor of biological sciences, recently published a paper uncovering part of the process that controls this compartmentalization.
The researchers discovered that SNARE proteins are modified with a small protein tag called ubiquitin, which helps determine where cargo is sent. They determined that ubiquitin could be bound by a protein called COPI, which is found on the surface of some vesicles, and that this interaction is critical for recruiting different SNARE proteins. As far as they know, they are currently the only labs worldwide addressing how ubiquitin’s interactions with COPI control SNARE trafficking.
WHY IT MATTERS
The proper localization of SNAREs is essential for cell viability, and defects in this process are associated with neurodegenerative diseases such as Alzheimer’s disease, Parkinson’s disease and amyotrophic lateral sclerosis (also known as Lou Gehrig’s disease). In addition, many viruses—including SARS-CoV-2, the virus that causes COVID-19—use cells’ cargo-sorting machinery during the infection or virus formation processes. A better understanding of the basic functions of this intracellular transport system could aid in disease prevention.
WHAT COMES NEXT
The Graham, MacGurn and Jackson labs are currently working on new tools that will help identify factors that control SNARE ubiquitination and function and vesicle transport. The researchers will use these tools to continue investigating how the organization of a cell is determined and maintained. This information could be used to determine mechanisms that govern viral replication, organelle maintenance and general cell health.
These studies were supported by the National Institutes of Health and The Pew Charitable Trusts.
The article “Ubiquitination drives COPI priming and Golgi SNARE localization” was published in eLife in July 2022.