UI researchers discover new mechanism controlling movement of cell structures
Organelles are compartments and structures inside cells that perform varied and vital functions, including energy production, storage and transportation of important substances and removal of waste products. Normal cellular function requires that organelles be positioned in specific locations in a cell. Thus, movement of the organelles to their appropriate destinations is critical.
A team of University of Iowa researchers has discovered a new mechanism that helps explain how organelles are delivered to the right place at the right time. The research findings appear in the Feb. 16 Nature Advance Online Publication.
Understanding how organelles get to their assigned cellular locations will improve understanding of embryonic development and may have implications for understanding many diseases including cancer and diabetes, said Lois Weisman, Ph.D., UI associate professor of biochemistry and principal investigator of the study.
Weisman and her colleagues made their discovery by studying organelle movement in yeast. The team identified a protein that specifically couples vacuoles (yeast organelles) to the organelle transportation system and also appears to plays a key role in controlling the timing and delivery of the vacuole to its final destination.
Most yeast proteins have direct humans counterparts known as homologs. This similarity makes yeast a good experimental organism because almost everything researchers learn about yeast cells is likely to be applicable to human cells, too. In addition, manipulating and analyzing yeast genes is much easier and faster than working with higher life forms.
The machinery that moves vacuoles in yeast also moves other organelles, as well. One question that interested Weisman and her colleagues was: how can this same mechanism move different organelles to different locations at different times?
The transport system acts like a cable car with motor molecules transporting organelles through the cell along cable-like structures. The protein discovered by the UI team specifically couples vacuoles to a motor molecule. The studies also suggest that when the vacuole arrives at its correct destination, the coupling protein is degraded, which causes the vacuole to be deposited in the right location.
"The protein we have discovered is called Vac17p. We found that it is involved in the specific coupling of vacuoles to the motor protein," Weisman said. "More surprisingly, we also found that regulation of the appearance and disappearance of this protein controls when that organelle moves and where it moves to."
Working with various yeast mutants, Fusheng Tang, Ph.D., UI postdoctoral researcher and lead author of the study, discovered that if the Vac17p protein does not get degraded, then the release mechanism is disrupted and the vacuole is not deposited in the correct cellular location. His research suggests that the controlled assembly and disassembly of the molecular transport complexes is critical for accurate and directed organelle movement.
"We were just trying to figure out how the specific coupling mechanism worked and then we also discovered this protein turnover mechanism, which seems to be critical for depositing the cargo at the right place and time," Weisman said.
Because the organelle transport system in yeast is essentially the same as the system found in higher animals including humans, the researchers believe that regulated disassembly of organelle transportation complexes may be a general mechanism for moving organelles to their final cellular destinations in all cells.
In addition to Weisman and Tang, other UI researchers involved in the study included research assistants, Emily Kauffman, Jennifer Novak and Johnathan Nau, and Natalie Catlett, Ph.D., who was a graduate student in Weisman’s lab.
The research was funded by grants from the National Institutes of Health and the National Science Foundation.
Source: University of Iowa, February 2003