The adaptor protein chaperone AAGAB stabilizes AP-4 complex subunits.

Area of Science:

• Cell biology
• Molecular biology
• Neuroscience

Background:

• Adaptor protein 4 (AP-4) is crucial for cargo export from the trans-Golgi network (TGN).
• AP-4 mutations cause hereditary spastic paraplegia (AP-4-deficiency syndrome).
• AP-4 complex assembly mechanisms were previously unknown.

Purpose of the Study:

• To elucidate the mechanisms of AP-4 complex assembly.
• To identify proteins involved in AP-4 subunit stabilization and complex formation.

Main Methods:

• Investigated the interaction between AAGAB and AP-4 subunits.
• Utilized AAGAB-knockout cell models to assess AP-4 levels and cargo trafficking.

Main Results:

• AAGAB binds to and stabilizes AP-4 ε and σ4 subunits, promoting AP-4 complex assembly.
• AAGAB-knockout cells show reduced AP-4 levels and ATG9A accumulation at the TGN.
• These cellular phenotypes mirror those observed in AP-4-deficiency syndrome.

Conclusions:

• AP-4 complex assembly requires AAGAB assistance.
• AAGAB plays a critical role in AP-4 function and cellular trafficking.
• Findings advance understanding of AP-4-deficiency syndrome and CNS development.