Associate Professor Rohan Teasdale
The University of Queensland
Parkinson Disease associated retromer variants alter endosomal trafficking pathways.
Retromer is a peripheral protein complex that coordinates multiple vesicular trafficking events within the endo-lysosomal system. Here, we demonstrate that retromer is required for the maintenance of normal lysosomal function. At the whole cell level, the knockout of retromer Vps35 subunit reduces the lysosomal proteolytic capacity, as a consequence of the improper processing of lysosomal hydrolases, dependent on the cation-independent mannose 6-phophate receptor (CI-M6PR) trafficking. Moreover, we identify that CI-M6PR, sorted via the retromer-dependent process, is incorporated into a subset of endosome transport carriers (ETCs) tethered by a specific trans-Golgi protein. Finally, we demonstrate that the formation of these subset of endosome transport carriers (ETCs) are not formed when only the Parkinson Disease causing variant of Vps35 is present in cells.
Rohan Teasdale is currently a T&R academic within the School of Biomedical Sciences at the University of Queensland. He gained his PhD at Monash University in cell biology and while as a postdoctoral scientist at RW Johnson PRI, a Johnson and Johnson company in San Diego he gained expertise in bioinformatics. Upon returning to Australia my focus has been on the characterisation of the mammalian endosomal system and the trafficking pathways originating from within this highly dynamic intracellular organelle. His Protein Trafficking in Disease research group has made key contributions including the discovery of the retromer protein complex that is a central regulator of early endosome protein trafficking and the PX/SNX family of proteins. Retromer has been recently implicated in neurodegeneration, including Parkinson’s disease and we are investigating the molecular mechanisms underlying how its dysfunction causes Parkinson’s Disease.