University of Dundee

Mechanistic insights into the cellular delivery of proteins

31 May 2022

Recent research from David Murray and Hannes Maib has uncovered key mechanistic insights into the delivery of proteins in cells. This work has been published in Current Biology.  

Cells are the basic building block of life and come in many shapes and forms. From neurons that can be multiple feet long to the epithelial cells that make up our skin, all cells are surrounded by a thin membrane that separates them from other cells and the outside world. Importantly, specialised proteins need to be delivered to these cellular membranes to ensure that the cells stay healthy and fulfil their unique roles. For example, in neurons this delivery process ensures that connections are formed in our brain. To achieve this delivery, proteins are packed into small cargo vesicles that get distributed throughout the cell to the correct destination (like a parcel of nicely packed chocolates delivered by the postman). This process of delivering proteins to cellular membrane is crucial for healthy cellular functions and often misregulated in disease.  

“Our research has uncovered key mechanistic insight into the molecular machinery that ensures that the correct proteins are delivered to the correct destination of the cell. We were able to replicate key stages of this process in the test tube, determining how cargo vesicles are recognised and tethered to the outer membrane in the final step of their journey throughout the cell. These findings provide key insights into a fundamental process of cells and may form the foundation for more translational studies,” explained David Murray, Principal Investigator and Wellcome Trust Sir Henry Dale Fellow in the Division of Cell and Developmental Biology. 

“A better understanding of this fundamental mechanism of cell biology may enable future works to target the pathway we have studied, potentially shifting cellular and thereby tissue phenotypes. These advances in basic research are crucial to gain a better understanding of how our cells work, so that we may better understand what exactly happens in disease when they don’t work as they should.” 

This work was supported by funding from the Wellcome Trust, Royal Society, Tenovus Scotland and SULSA.  

Read ‘A mechanism for exocyst-mediated tethering via Arf6 and PIP5K1C-driven phosphoinositide conversion’.