TCDB is operated by the Saier Lab Bioinformatics Group

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 mis-sorting 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.

References associated with 9.B.278 family:

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. 30262884
Guardia, C.M., R. De Pace, R. Mattera, and J.S. Bonifacino. (2018). functions of adaptor complexes involved in protein sorting. Curr Opin Neurobiol 51: 103-110. [Epub: Ahead of Print] 29558740
He, X., F. Li, W.P. Chang, and J. Tang. (2005). GGA proteins mediate the recycling pathway of memapsin 2 (BACE). J. Biol. Chem. 280: 11696-11703. 15615712
Kang, E.L., A.N. Cameron, F. Piazza, K.R. Walker, and G. Tesco. (2010). Ubiquitin regulates GGA3-mediated degradation of BACE1. J. Biol. Chem. 285: 24108-24119. 20484053
Lau, A.W. and M.M. Chou. (2008). The adaptor complex AP-2 regulates post-endocytic trafficking through the non-clathrin Arf6-dependent endocytic pathway. J Cell Sci 121: 4008-4017. 19033387
Marcello, E., C. Saraceno, S. Musardo, H. Vara, A.G. de la Fuente, S. Pelucchi, D. Di Marino, B. Borroni, A. Tramontano, I. Pérez-Otaño, A. Padovani, M. Giustetto, F. Gardoni, and M. Di Luca. (2013). Endocytosis of synaptic ADAM10 in neuronal plasticity and Alzheimer's disease. J Clin Invest 123: 2523-2538. 23676497
Mattera, R., C.D. Williamson, X. Ren, and J.S. Bonifacino. (2020). The FTS-Hook-FHIP (FHF) complex interacts with AP-4 to mediate perinuclear distribution of AP-4 and its cargo ATG9A. Mol. Biol. Cell 31: 963-979. 32073997
Mulholland, P.J., S. Berto, P.A. Wilmarth, C. McMahan, L.E. Ball, and J.J. Woodward. (2023). Adaptor protein complex 2 in the orbitofrontal cortex predicts alcohol use disorder. bioRxiv. 37398482
Nakatsu, F. and H. Ohno. (2003). Adaptor protein complexes as the key regulators of protein sorting in the post-Golgi network. Cell Struct Funct 28: 419-429. 14745134
Owen, D.J., B.M. Collins, and P.R. Evans. (2004). Adaptors for clathrin coats: structure and function. Annu. Rev. Cell Dev. Biol. 20: 153-191. 15473838
Paing, M.M., C.A. Johnston, D.P. Siderovski, and J. Trejo. (2006). Clathrin adaptor AP2 regulates thrombin receptor constitutive internalization and endothelial cell resensitization. Mol. Cell Biol. 26: 3231-3242. 16581796
Partlow, E.A., R.W. Baker, G.M. Beacham, J.S. Chappie, A.E. Leschziner, and G. Hollopeter. (2019). A structural mechanism for phosphorylation-dependent inactivation of the AP2 complex. Elife 8:. 31464684
Puertollano, R., P.A. Randazzo, J.F. Presley, L.M. Hartnell, and J.S. Bonifacino. (2001). The GGAs promote ARF-dependent recruitment of clathrin to the TGN. Cell 105: 93-102. 11301005
Roach, T.G., H.K.M. Lång, W. Xiong, S.J. Ryhänen, and D.G.S. Capelluto. (2021). Protein Trafficking or Cell Signaling: A Dilemma for the Adaptor Protein TOM1. Front Cell Dev Biol 9: 643769. 33718385
Tesco, G., Y.H. Koh, E.L. Kang, A.N. Cameron, S. Das, M. Sena-Esteves, M. Hiltunen, S.H. Yang, Z. Zhong, Y. Shen, J.W. Simpkins, and R.E. Tanzi. (2007). Depletion of GGA3 stabilizes BACE and enhances β-secretase activity. Neuron. 54: 721-737. 17553422
Uemura, T. and S. Waguri. (2019). Emerging roles of Golgi/endosome-localizing monomeric clathrin adaptors GGAs. Anat Sci Int. [Epub: Ahead of Print] 31659673
Zhang, M., J.E. Davis, C. Li, J. Gao, W. Huang, N.A. Lambert, A.V. Terry, Jr, and G. Wu. (2016). GGA3 Interacts with a G Protein-Coupled Receptor and Modulates Its Cell Surface Export. Mol. Cell Biol. 36: 1152-1163. 26811329