Role of adaptin protein complexes in intracellular trafficking and their impact on diseases

Abstract

Adaptin proteins (APs) play a crucial role in intracellular cell trafficking. The 'classical' role of APs is carried out by AP1-3, which bind to clathrin, cargo, and accessory proteins. Accordingly, AP1-3 are crucial for both vesicle formation and sorting. All APs consist of four subunits that are indispensable for their functions. In fact, based on studies using cells, model organism knockdown/knock-out, and human variants, each subunit plays crucial roles and contributes to the specificity of each AP. These studies also revealed that the sorting and intracellular trafficking function of AP can exert varying effects on pathology by controlling features such as cell development, signal transduction related to the apoptosis and proliferation pathways in cancer cells, organelle integrity, receptor presentation, and viral infection. Although the roles and functions of AP1-3 are relatively well studied, the functions of the less abundant and more recently identified APs, AP4 and AP5, are still to be investigated. Further studies on these APs may enable a better understanding and targeting of specific diseases.

When less is more – A fast TurboID KI approach for high sensitivity endogenous interactome mapping

“…Although AP-1, AP-3 and AP-4 are all known to be recruited by ARF1 to TGN/endosomal membranes 34 , they localise to distinct endosomal buds 35,36 , suggesting the presence of different unknown interactors. Due to their role as key regulators of intracellular trafficking, dysfunction of AP complexes is linked to a variety of diseases 31,34,37 and a better understanding of the interaction partners could help revealing the underlying mechanistic basis of pathology. While AP-1 is known to locate to the TGN and endosomal membranes 20,36,38 where it coordinates clathrin-dependent trafficking between the two organelles 19,39,40 , AP-2 can be found at the plasma membrane where it recruits clathrin for clathrin-mediated endocytosis 19 .…”

Identification of peripheral blood immune infiltration signatures and construction of monocyte-associated signatures in ovarian cancer and Alzheimer's disease using single-cell sequencing

“…AP1S2 has been reported as a prognostic marker in ovarian cancer, and its expression levels differ in drug-resistant cell lines [ 72 ]. In melanoma, downregulation of AP1S2 inhibits tumor cell migration, indicating its potential as a therapeutic target [ 73 ]. However, there are no studies on AP1S2 in neurodegenerative diseases, although mutations in AP1S2 have been noted in cases of fourth ventricular foramen occlusion syndrome with intellectual disability, basal ganglia disease, and seizures [ 74 ].…”

Genome-wide epigenetic modifications in sports horses during training as an adaptation phenomenon

“…The expression of the AP5Z1 gene, encoding a crucial protein for intracellular cell trafficking by controlling features such as cell development, signal transduction, apoptosis, and proliferation pathways 41 , is instead modulated accordingly with its methylation state in different libraries. Like the TTC7A gene (up-regulated in leukocytes of the T90 library compared to T30 and de-methylated in the same comparison) that encodes a scaffolding protein, facilitating the synthesis of PI4-phosphate (PI4P) essential for promoting transport of secretory proteins 42 .…”