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.

This family belongs to the .



Davies, A.K., D.N. Itzhak, J.R. Edgar, T.L. Archuleta, J. Hirst, L.P. Jackson, M.S. Robinson, and G.H.H. Borner. (2018). AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A. Nat Commun 9: 3958.

Guardia, C.M., R. De Pace, R. Mattera, and J.S. Bonifacino. (2018). Neuron.al functions of adaptor complexes involved in protein sorting. Curr Opin Neurobiol 51: 103-110. [Epub: Ahead of Print]


TC#NameOrganismal TypeExample

The Adaptor Protein Complex, AP1 with subunits β1 (AP1B1, 949 aas), γ1 (AP1G1, 822 aas), μ1 (AP1M1; 423 aas) and σ1 (AP1S1, 158 aas).  Subunits of clathrin-associated adaptor protein complex 1 form a complex that plays a role in protein sorting in the late-Golgi/trans-Golgi network (TGN) and/or endosomes. The AP complexes mediate both the recruitment of clathrin to membranes and the recognition of sorting signals within the cytosolic tails of transmembrane cargo molecules (Guardia et al. 2018). These complexes therefore play a role in protein insertion into organellar membranes.  There is one isoform of β1, two of γ1, two of
μ1, and three of σ1. Only one iso-form of each is included here.  Although there are 5 such complexes in humans (AP-1 - 5), and many eukaryotic organisms have one of more of them, only AP1 of humans is tabulated in TCDB (Guardia et al. 2018). Parts of subunits β1 and γ1 are homologous, and parts of subunits μ1 and σ1 show significant sequence similarity, suggestiong homology.

AP1 complex of Homo sapiens