Abstract
Intracellular membrane traffic is coordinated by Rab GTPases and their effector proteins. Here, we investigated the function in human cells of Tumor Protein D54 (TPD54/TPD52L2), a member of the TPD52-like protein family. Our initial experiments suggested that TPD54 has a role in anterograde membrane traffic and in the recycling of endocytosed proteins back to the cell surface. To understand how TPD54 controls these diverse functions, we used an inducible method to reroute TPD54 to mitochondria. Surprisingly, this manipulation resulted in the capture of many functional vesicles (30nm diameter) at the mitochondrial surface. To investigate the identity of captured vesicles, we did a rerouting screen using TPD54 as bait and the Rab GTPases as prey. This screen revealed that TPD54 associates promiscuously with at least 16 out of 43 different Rab GTPases. Our data suggest that TPD54 binds as an effector protein to Rabs involved in anterograde traffic and recycling where it likely promotes vesicle fusion.
Footnotes
Addition of Figure 10 to show effect of TPD54 knockout on fusion.