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8.A.203.  The Adaptor Protein 4 Chaparone (AAGAB) Family 

The adaptor protein chaperone, AAGAB, stabilizes AP-4 complex subunits (Mattera et al. 2022). Adaptor protein 4 (AP-4) is a heterotetrameric complex composed of epsilon, beta4, mu4, and sigma4 subunits that mediates export of a subset of transmembrane cargos, including autophagy protein 9A (ATG9A), from the trans-Golgi network (TGN). AP-4 has received attention because mutations in any of its subunits cause a complicated form of hereditary spastic paraplegia referred to as "AP-4-deficiency syndrome." The identification of proteins that interact with AP-4 has revealed the mechanisms of AP-4-dependent cargo sorting and distribution within the cell. Mattera et al. 2022 reported that the alpha- and gamma-adaptin-binding protein (AAGAB, also known as p34) binds to and stabilizes the AP-4 epsilon and sigma4 subunits, thus promoting complex assembly. The physiological importance of these interactions is underscored by the observation that AAGAB-knockout cells exhibit reduced levels of AP-4 subunits and accumulation of ATG9A at the TGN like those in cells with mutations in AP-4-subunit genes. Thus, AP-4 assembly is not spontaneous but AAGAB-assisted, further contributing to the understanding of an adaptor protein complex that is critically involved in development of the central nervous system (Mattera et al. 2022).

References associated with 8.A.203 family:

Amores-Bonet, L., R. Kleene, T. Theis, and M. Schachner. (2022). Interactions between the Polysialylated Neural Cell Adhesion Molecule and the Transient Receptor Potential Canonical Channels 1, 4, and 5 Induce Entry of Ca into Neuron.s. Int J Mol Sci 23:. 36077460
Mattera, R., R. De Pace, and J.S. Bonifacino. (2022). The adaptor protein chaperone AAGAB stabilizes AP-4 complex subunits. Mol. Biol. Cell 33: ar109. 35976721
Pohler, E., O. Mamai, J. Hirst, M. Zamiri, H. Horn, T. Nomura, A.D. Irvine, B. Moran, N.J. Wilson, F.J. Smith, C.S. Goh, A. Sandilands, C. Cole, G.J. Barton, A.T. Evans, H. Shimizu, M. Akiyama, M. Suehiro, I. Konohana, M. Shboul, S. Teissier, L. Boussofara, M. Denguezli, A. Saad, M. Gribaa, P.J. Dopping-Hepenstal, J.A. McGrath, S.J. Brown, D.R. Goudie, B. Reversade, C.S. Munro, and W.H. McLean. (2012). Haploinsufficiency for AAGAB causes clinically heterogeneous forms of punctate palmoplantar keratoderma. Nat. Genet. 44: 1272-1276. 23064416