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The WDR11 complex is a receptor for acidic-cluster-containing cargo proteins
Huaqing Deng1, Guowen Jia2, Ping Li1
1Key Laboratory of Birth Defects and Related Diseases of Women and Children, Department of Paediatrics, West China Second University Hospital, State Key Laboratory of Biotherapy, Sichuan University, Chengdu 610041, China.
Cell
|July 16, 2024
Summary
The WDR11-FAM91A1 complex recognizes specific acidic clusters on proteins, ensuring accurate cargo sorting during vesicle transport. This mechanism is crucial for neuronal development, revealing a new layer of protein recognition in cellular trafficking.
Area of Science:
- Cell Biology
- Molecular Biology
- Neuroscience
Background:
- Vesicle trafficking is essential for sorting and transporting proteins within eukaryotic cells.
- Cargo recognition typically involves protein coats at the donor membrane.
- The role of cargo selection at later stages of vesicle trafficking remains largely unknown.
Purpose of the Study:
- To investigate the mechanism of cargo recognition downstream of the AP-1 complex.
- To elucidate the function of the WDR11-FAM91A1 complex in protein transport.
- To understand the implications of this mechanism for neuronal development.
Main Methods:
- Cryo-electron microscopy (cryo-EM) to determine the structure of the WDR11-FAM91A1 complex.
- Biochemical assays to study the binding of WDR11 to acidic clusters.
- Zebrafish models to assess the in vivo function of the WDR11-FAM91A1 complex.
Main Results:
- The cryo-EM structure of the human WDR11-FAM91A1 complex was determined.
- WDR11 was found to directly and specifically recognize "super acidic clusters" (SACs) on cargo proteins.
- WDR11-FAM91A1 complex assembly and SAC binding are vital for trafficking SAC-containing proteins and proper zebrafish neuronal development.
Conclusions:
- Cargo proteins can be recognized in a sequence-specific manner downstream of a protein coat.
- The WDR11-FAM91A1 complex provides a mechanism for enhanced fidelity in vesicle trafficking.
- This discovery offers new insights into the regulation of protein transport and its role in neuronal development.
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