Two distinct regulatory pathways govern Cct2-Atg8 binding in the process of solid aggrephagy

Area of Science:

• Cell Biology
• Molecular Biology
• Autophagy Research

Background:

• CCT2 is an aggrephagy receptor essential for clearing solid aggregates.
• The precise molecular mechanisms of CCT2 in solid aggrephagy are not fully elucidated.

Purpose of the Study:

• To investigate the molecular mechanisms governing CCT2's interaction with Atg8 in solid aggrephagy.
• To identify regulatory factors controlling CCT2 function in autophagy.

Main Methods:

• Investigated CCT2 phosphorylation by Atg1 at specific serine residues (Ser412, Ser470).
• Examined the interaction between CCT2 and the selective autophagy adaptor protein Atg11.
• Assessed the impact of disrupted phosphorylation sites and CCT2-Atg11 interaction on CCT2-Atg8 binding and aggrephagy.
• Validated findings in mammalian cell models.

Main Results:

• Atg1-mediated phosphorylation of CCT2 at Ser412 and Ser470 is crucial for CCT2-Atg8 binding and solid aggrephagy.
• Atg11 directly binds to CCT2 via its CC4 domain, facilitating CCT2-Atg8 association.
• Disruption of these regulatory mechanisms impairs solid aggrephagy.
• The identified mechanisms are conserved in mammalian cells.

Conclusions:

• Atg1-mediated CCT2 phosphorylation and Atg11-CCT2 interaction are key regulators of CCT2-Atg8 binding in solid aggrephagy.
• These findings provide novel insights into the molecular control of selective autophagy.
• The conserved nature of these mechanisms highlights their fundamental importance in cellular protein quality control.