AP1AR (adaptor-related protein complex 1-associated regulatory protein), also known as C4orf16 or Gamma-BAR, is a human protein critical for AP-1-dependent intracellular transport between the trans-Golgi network and endosomes . It regulates membrane association of the AP-1 adapter complex, particularly interacting with AP1G1/Gamma1-adaptin to stabilize its membrane attachment . This interaction is vital for calcium-induced endo-lysosomal secretion and attenuates AP-1 complex release from membranes .
AP1AR acts as a critical regulator of vesicular trafficking and membrane dynamics:
AP-1 Complex Stabilization: Directly binds AP1G1 to inhibit its dissociation from membranes, ensuring sustained AP-1 activity in endosomal sorting .
Calcium-Dependent Secretion: Facilitates calcium-triggered secretion of lysosomal contents, linking AP-1 function to cellular signaling .
Kinesin Interaction: Associates with kinesin motor proteins, suggesting a role in microtubule-dependent transport .
AP1AR is studied using diverse experimental approaches:
Product | Use Case | Source |
---|---|---|
Full-Length AP1AR | Protein-protein interaction studies | Prospec Bio |
aa 2-82 Fragment | Antibody blocking assays (e.g., PA5-57436) | Thermo Fisher |
Thermo Fisher’s recombinant fragment is used to validate antibody specificity in IHC/ICC/WB experiments .
AP1AR Adenovirus: Enables transient overexpression in cell lines for studying AP-1-dependent trafficking.
Antibody | Immunogen | Ortholog Identity |
---|---|---|
PA5-57436 (Polyclonal) | GNCCWTQCFG... (aa 2-82) | Mouse (90%), Rat (94%) |
This antibody is validated for IHC/ICC and WB, with controls using recombinant AP1AR fragments .
AP1AR interacts with >4,000 biological entities, as mapped by the Harmonizome database :
Category | Key Associations |
---|---|
Co-expressed Genes | AP1G1, VAMP3 (vesicular transport) |
Protein Interactions | AP-1 complex subunits, kinesin family members |
Disease Links | Neurological disorders, cancer (expression modulation) |
Cellular Localization | Golgi, endosomes, cytoplasm |
AP1AR expression is tissue-specific, with elevated levels in brain, liver, and kidney .
AP1AR expression and activity are influenced by:
Chemical Modulators:
Post-translational Modifications: Phosphorylation (e.g., by kinase inhibitors) and acetylation .
While direct disease links remain under investigation, AP1AR’s role in endosomal trafficking implicates it in:
The AP1AR gene is located on chromosome 4q25 and encodes a protein consisting of 302 amino acids . The protein contains a coiled-coil region, which is essential for its interaction with other proteins, such as AP1G1 (gamma1-adaptin), a subunit of the AP-1 adaptor complex . This interaction is critical for the regulation of membrane association and the release of the AP-1 complex from membranes .
AP1AR is necessary for AP-1-dependent transport between the TGN and endosomes . It regulates the membrane association of AP1G1/gamma1-adaptin by directly interacting with it, which attenuates the release of the AP-1 complex from membranes . This regulation is crucial for maintaining proper intracellular trafficking and ensuring that proteins are correctly sorted and transported within the cell .
Additionally, AP1AR is involved in the negative regulation of receptor recycling and vesicle targeting from the trans-Golgi to endosomes . It also plays a role in linking kinesin-based plus-end-directed microtubular transport to AP-1-dependent membrane traffic . This linkage is essential for the proper functioning of intracellular transport mechanisms and the maintenance of cellular homeostasis .
The proper functioning of AP1AR is vital for various cellular processes, including endosomal membrane traffic and calcium-induced endo-lysosome secretion . It also inhibits the Arp2/3 complex function, negatively regulating cell spreading, size, and motility via intracellular sequestration of the Arp2/3 complex . These regulatory functions highlight the importance of AP1AR in maintaining cellular dynamics and ensuring the proper distribution of cellular components .
Research on AP1AR has provided insights into its role in intracellular trafficking and its potential implications in various diseases. For instance, dysregulation of AP1AR function could lead to defects in protein sorting and transport, contributing to the development of certain diseases . Understanding the mechanisms by which AP1AR regulates intracellular trafficking could pave the way for developing therapeutic strategies targeting these pathways.