Opposing roles of RUBCN isoforms in autophagy and memory B cell generation

Area of Science:

• Cell Biology
• Immunology

Background:

• Rubicon (RUBCN) was initially identified as a negative regulator of autophagy.
• Autophagy is a cellular degradation process crucial for recycling damaged components.
• Autophagy involves the class III PI3K VPS34 and the mTORC1 protein complex.

Purpose of the Study:

• To characterize the role of a shorter RUBCN isoform, RUBCN100, in B cells.
• To investigate the opposing functions of RUBCN isoforms in autophagy and B cell differentiation.

Main Methods:

• Investigated RUBCN100 function in B cells.
• Analyzed RUBCN isoform localization and effects on VPS34 activity.
• Examined RUBCN isoform impact on autophagy and mTORC1 signaling.

Main Results:

• RUBCN100, translated from alternative sites, lacks the RUN domain found in RUBCN130.
• RUBCN130 deficiency in B cells enhanced autophagy and memory B cell generation.
• RUBCN100 localized to early endosomes, enhancing VPS34 activity, while RUBCN130 localized to late endosomes/lysosomes, suppressing VPS34.
• RUBCN100 promoted autophagy and suppressed mTORC1 activation, unlike RUBCN130.

Conclusions:

• Opposing roles of RUBCN100 and RUBCN130 isoforms are critical for regulating autophagy.
• These opposing functions are essential for memory B cell differentiation.