Getting a handle on RAB1: from Golgi trafficking to mitophagy

The small GTPase RAB1 is essential for life. A knockout of RAB1 is not only embryonically lethal, but even triggers cell death in a cultured cell line, underscoring its importance for cellular homeostasis. Previous work has shown that RAB1 plays a key role in protein and membrane trafficking as a player in the ER-to-Golgi trafficking pathway. Here, RAB1 has been shown to interact with COPII vesicles that have left the ER and are arriving at the Golgi. In addition, RAB1 is an essential part of autophagy initiation, where loss of RAB1 leads to defects very early in the pathway. To complicate matters further, there is a non-trivial overlap in phenotype between a Golgi trafficking defect and an autophagy initiation problem, as ATG9A vesicle trafficking and the general importance of the Golgi in autophagy illustrates. Given these hurdles, how would one get a handle on the molecular mechanism of RAB1? In this Punctum, I discuss our recent mapping of a new RAB1 interactome that provides fresh insights into its multifaceted functions.