Formation of autophagosomes requires vesicular trafficking from virtually every subcellular compartment to the formation site. This traffic must be tightly regulated but also adaptable as different membrane compartments will contribute varying amounts of membrane, lipids and proteins to the forming autophagosome depending on the stimulus. In mammalian cells, efforts to understand how autophagosomes form have been focused on the role of Rab proteins in autophagy. Rab proteins provide specificity through their interaction with coat proteins, vesicle tethers and SNAREs. Recent data emerging from these studies have defined a subset of Rab proteins and their regulators, the RabGAPS (GTPase activating proteins) in both autophagosome formation and maturation. This review will focus on the role of a set of RabGAPs shown to regulate autophagy, in particular TBC1D14, and its interactors, RAB11 and TRAPPIII. Through our studies on TBC1D14, we have gained an understanding of the contribution of membrane from the recycling endosome, and the role of TRAPPIII in maintaining ATG (Autophagy protein) 9 trafficking in autophagosome formation.
Keywords: ATG9; Rab proteins; TBC domains; TRAPPIII; autophagosome; autophagy.