An AAGAB-to-CCDC32 handover mechanism controls the assembly of the AP2 adaptor complex.

Autor:	Wan C; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309., Puscher H; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309., Ouyang Y; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309., Wu J; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309., Tian Y; Department of Biological Sciences and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306., Li S; Department of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80045., Yin Q; Department of Biological Sciences and Institute of Molecular Biophysics, Florida State University, Tallahassee, FL 32306., Shen J; Department of Molecular, Cellular and Developmental Biology, University of Colorado, Boulder, CO 80309.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Aug 20; Vol. 121 (34), pp. e2409341121. Date of Electronic Publication: 2024 Aug 15.
DOI:	10.1073/pnas.2409341121
Abstrakt:	Vesicular transport relies on multimeric trafficking complexes to capture cargo and drive vesicle budding and fusion. Faithful assembly of the trafficking complexes is essential to their functions but remains largely unexplored. Assembly of AP2 adaptor, a heterotetrameric protein complex regulating clathrin-mediated endocytosis, is assisted by the chaperone AAGAB. Here, we found that AAGAB initiates AP2 assembly by stabilizing its α and σ2 subunits, but the AAGAB:α:σ2 complex cannot recruit additional AP2 subunits. We identified CCDC32 as another chaperone regulating AP2 assembly. CCDC32 recognizes the AAGAB:α:σ2 complex, and its binding leads to the formation of an α:σ2:CCDC32 ternary complex. The α:σ2:CCDC32 complex serves as a template that sequentially recruits the µ2 and β2 subunits of AP2 to complete AP2 assembly, accompanied by CCDC32 release. The AP2-regulating function of CCDC32 is disrupted by a disease-causing mutation. These findings demonstrate that AP2 is assembled by a handover mechanism switching from AAGAB-based initiation complexes to CCDC32-based template complexes. A similar mechanism may govern the assembly of other trafficking complexes exhibiting the same configuration as AP2. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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