AAGAB is an assembly chaperone regulating AP1 and AP2 clathrin adaptors

Area of Science:

• Cell Biology
• Molecular Biology
• Biochemistry

Background:

• Multimeric cargo adaptors like AP2 are essential for intracellular membrane trafficking.
• Clathrin-mediated endocytosis relies on adaptor complexes for cargo selection and vesicle formation.

Purpose of the Study:

• To investigate the role of alpha- and gamma-adaptin-binding protein (AAGAB) in the assembly of adaptor complexes beyond AP2.
• To elucidate the function of AAGAB in AP1 complex formation and its impact on cellular processes.

Main Methods:

• Co-immunoprecipitation assays to study protein interactions.
• Mutational analysis of AAGAB to assess its role in adaptor complex assembly.
• Comparative proteomic analysis to evaluate surface protein homeostasis.
• Functional assays to assess AP1-mediated cargo trafficking.

Main Results:

• AAGAB regulates the assembly of both AP1 and AP2 adaptor complexes, but not AP3.
• AAGAB directly binds and stabilizes the gamma and sigma subunits of AP1.
• AAGAB mutation disrupts AP1 assembly and AP1-mediated cargo trafficking.
• Loss of AAGAB function leads to altered surface protein homeostasis, reflecting combined AP1 and AP2 deficiency.

Conclusions:

• AAGAB functions as a critical assembly chaperone for both AP1 and AP2 adaptor complexes.
• AAGAB's role in AP1 and AP2 assembly is essential for maintaining cellular protein homeostasis.
• Understanding AAGAB's function provides insights into the pathogenesis of AAGAB-linked diseases.