9.B.278. The Organellar-targeting Adaptor Protein Complex (O-APC) Family
Selective transport of transmembrane proteins to different intracellular compartments often involves the recognition of sorting signals in the cytosolic domains of the proteins by components of membrane coats. Some of these coats have as their key components a family of heterotetrameric adaptor protein (AP) complexes named AP-1 through AP-5. AP complexes play important roles in all cells, but their functions are most critical in neurons because of the extreme compartmental complexity of these cells. Accordingly, various diseases caused by mutations in AP subunit genes exhibit a range of neurological abnormalities as their most salient features.Guardia et al. 2018 discussed the properties of the different AP complexes, with a focus on their roles in neuronal physiology and pathology. AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A (Davies et al. 2018). Three transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, and two AP-4 accessory proteins, RUSC1 and RUSC2 are involved. Davies et al. 2018 demonstrated that AP-4 deficiency causes missorting of ATG9A in diverse cell types as well as dysregulation of autophagy. RUSC2 facilitates the transport of AP-4-derived, ATG9A-positive vesicles from the trans-Golgi network to the cell periphery. These vesicles cluster in close association with autophagosomes, suggesting they are the 'ATG9A reservoir' required for autophagosome biogenesis.